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Cardiovascular Medicine Treatment Treat patients with palpitations, chest pain, anxiety, or fatigue with p-blockers. Surgery is required for significant MR. TESTYOURSELF A 2S-year old woman has palpitations. Cardiac examination is normal except for an isolated click. Echocardiography is also normal except for mild MR, and 24 hour ECG monitoring shows 728 isolated, unifocal PVCs. ANSWER: For management, choose to provide reassurance and counsel on lifestyle modification (reduction of caffeine and other stimulants). Prosthetic Heart Valves Characteristics Mechanical valves are more durable than bioprosthetic valves but require Iifelong anticoagulation. Prosthetic valves in the aortic position are more durable and less prone to thromboembolism than valves in the mitral position. Complications Common complications include structural valve deterioration, valve thrombosis, embolism, bleeding, and endocarditis. In the immediate postoperative period, valve dehiscence or dysfunction should be suspected in patients who develop acute HE Valve dysfunction is characterized by new cardiac symptoms, embolic phenomena, hemo\tic anemia (with schistocytes on periph eral blood smear), or new murmurs. If prosthetic valve dysfunction is suspected, TEE is the diagnostic procedure of choice. Anticoagulation Lifelong oral anticoagulation with warfarin is recommended for all patients with a mechanical prosthesis. Target INRs are: o 2.5 for an aortic prosthetic valve (bileaflet or current-generation single-tilting disc) without thromboembolism risk factors . 3.0 for ball-in-cage aortic prosthetic valve with thromboembolism risk factors . 3.0 for any mitral valve prosthesis Aspirin is not routinely added to anticoagulation therapy in patients with a mechanical prosthetic valve. Keep the following in mind:

o 2.5 for an aortic prosthetic valve (bileaflet or current-generation single-tilting disc) without thromboembolism risk factors . 3.0 for ball-in-cage aortic prosthetic valve with thromboembolism risk factors . 3.0 for any mitral valve prosthesis Aspirin is not routinely added to anticoagulation therapy in patients with a mechanical prosthetic valve. Keep the following in mind: o Interrupt anticoagulation in patients with a prosthetic heart valve before noncardiac or dental surg€:ry 6ut not cataract surgery). o For aortic valve prostheses, stop warfarin 4 to 5 days before the procedure and restart as soon as postprocedure control of bleeding allows. . In patients at high risk for thrombosis (mitral prostheses, multiple prosthetic valves, AF, or previous thromboembolic events), stop warfarin 4 to 5 days before surgery and begin bridging anticoagulation with IV heparin; resume IV heparin within 24 hours after surgery. Warfarin is also reinitiated after surgery and heparin is discontinued when INR is therapeutic. DOI{'T BE TRICKED o Do not choose long-term anticoagulation for patients with bioprosthetic heart valves. . Select only warfarin for anticoagulation of mechanical heart valves. Do not select a DOAC. 37

Endocrinology and Metabolism Treatment STUDY TABLET Management of Hyperglycemic Crisis: DKA and HHS Fluids lnsulin (Regular) Potassium Correction of Acidosis Assess for volume status, then Give regular insulin,0.1 U/kg, Assess for adequate kidney lf pH is <6.9, consider sodium give 0.9% saline lV at 1 Uh as an lV bolus, followed by function with adequate urine bicarbonate, 100 mEq in initially in all patients and 0.1 Uikglh as an lV infusion. output (approximately 400 mL of sterile water, and continue if patient is severely 50 mUh). potassium chloride, 20 mEq, lf plasma glucose level does infused over 2 hours. hypovolemic. Switch to 0.45% not decrease by 1 0% in the first l{ serum potassium is normal saline at 250-500 mUh lf pH is 6.9 or greater, do not houl give additional bolus of <3.3 mEq/L, do not start insulin; if corrected serum sodium give sodium bicarbonate. 0.1 4 U/kg and resume previous instead, give lV potassium level becomes normal or high. infusion rate. chloride, 20-30 mEq/h, through When plasma glucose level central line catheter until serum When plasma glucose level potassium level is >3.3 mEq/L. reaches 200 mg/dL in patients reaches 200 mg/dL in DKA and Then add 20-30 mEq of with DKA or 300 mg/dL in HHS 300 mg/dL in HHS, reduce potassium chloride to each liter in the setting of continued lV insulin to 0.02-0.05 U/kg/h and insulin, switch to 5oZ dextrose of lV fluids to keep serum maintain plasma glucose level potassium level in the 4-5 mEq/L with 0.45% saline at betvveen 150-200 mg/dL until range. 150-250 mUh to avoid anion gap acidosis is resolved hypoglycemia. in DKA. lf serum potassium level is >5.2 mEq/L, do not give Plasma glucose should be potassium chloride; instead, maintained between start insulin and lVfluids and 250-300 mg/dL in HHS until check serum potassium level patient is alert and every 2 hours. hyperosmolar state resolves.

Treatment STUDY TABLET Management of Hyperglycemic Crisis: DKA and HHS Fluids lnsulin (Regular) Potassium Correction of Acidosis Assess for volume status, then Give regular insulin,0.1 U/kg, Assess for adequate kidney lf pH is <6.9, consider sodium give 0.9% saline lV at 1 Uh as an lV bolus, followed by function with adequate urine bicarbonate, 100 mEq in initially in all patients and 0.1 Uikglh as an lV infusion. output (approximately 400 mL of sterile water, and continue if patient is severely 50 mUh). potassium chloride, 20 mEq, lf plasma glucose level does infused over 2 hours. hypovolemic. Switch to 0.45% not decrease by 1 0% in the first l{ serum potassium is normal saline at 250-500 mUh lf pH is 6.9 or greater, do not houl give additional bolus of <3.3 mEq/L, do not start insulin; if corrected serum sodium give sodium bicarbonate. 0.1 4 U/kg and resume previous instead, give lV potassium level becomes normal or high. infusion rate. chloride, 20-30 mEq/h, through When plasma glucose level central line catheter until serum When plasma glucose level potassium level is >3.3 mEq/L. reaches 200 mg/dL in patients reaches 200 mg/dL in DKA and Then add 20-30 mEq of with DKA or 300 mg/dL in HHS 300 mg/dL in HHS, reduce potassium chloride to each liter in the setting of continued lV insulin to 0.02-0.05 U/kg/h and insulin, switch to 5oZ dextrose of lV fluids to keep serum maintain plasma glucose level potassium level in the 4-5 mEq/L with 0.45% saline at betvveen 150-200 mg/dL until range. 150-250 mUh to avoid anion gap acidosis is resolved hypoglycemia. in DKA. lf serum potassium level is >5.2 mEq/L, do not give Plasma glucose should be potassium chloride; instead, maintained between start insulin and lVfluids and 250-300 mg/dL in HHS until check serum potassium level patient is alert and every 2 hours. hyperosmolar state resolves. DON'T BE TRIGKED . DKA can present with abdominal pain. . Reducing the insulin infusion before complete clearing of ketones will cause a relapse of DKA. . Treatment of severe acidosis with bicarbonate is controversial, and evidence of benefit is lacking.

Treatment STUDY TABLET Management of Hyperglycemic Crisis: DKA and HHS Fluids lnsulin (Regular) Potassium Correction of Acidosis Assess for volume status, then Give regular insulin,0.1 U/kg, Assess for adequate kidney lf pH is <6.9, consider sodium give 0.9% saline lV at 1 Uh as an lV bolus, followed by function with adequate urine bicarbonate, 100 mEq in initially in all patients and 0.1 Uikglh as an lV infusion. output (approximately 400 mL of sterile water, and continue if patient is severely 50 mUh). potassium chloride, 20 mEq, lf plasma glucose level does infused over 2 hours. hypovolemic. Switch to 0.45% not decrease by 1 0% in the first l{ serum potassium is normal saline at 250-500 mUh lf pH is 6.9 or greater, do not houl give additional bolus of <3.3 mEq/L, do not start insulin; if corrected serum sodium give sodium bicarbonate. 0.1 4 U/kg and resume previous instead, give lV potassium level becomes normal or high. infusion rate. chloride, 20-30 mEq/h, through When plasma glucose level central line catheter until serum When plasma glucose level potassium level is >3.3 mEq/L. reaches 200 mg/dL in patients reaches 200 mg/dL in DKA and Then add 20-30 mEq of with DKA or 300 mg/dL in HHS 300 mg/dL in HHS, reduce potassium chloride to each liter in the setting of continued lV insulin to 0.02-0.05 U/kg/h and insulin, switch to 5oZ dextrose of lV fluids to keep serum maintain plasma glucose level potassium level in the 4-5 mEq/L with 0.45% saline at betvveen 150-200 mg/dL until range. 150-250 mUh to avoid anion gap acidosis is resolved hypoglycemia. in DKA. lf serum potassium level is >5.2 mEq/L, do not give Plasma glucose should be potassium chloride; instead, maintained between start insulin and lVfluids and 250-300 mg/dL in HHS until check serum potassium level patient is alert and every 2 hours. hyperosmolar state resolves. DON'T BE TRIGKED . DKA can present with abdominal pain. . Reducing the insulin infusion before complete clearing of ketones will cause a relapse of DKA. . Treatment of severe acidosis with bicarbonate is controversial, and evidence of benefit is lacking. Diabetes Care for Hospitalized Patients Treatment Insulin is the preferred treatment for achieving inpatient g$cemic control. Critically ill patients with type 2 diabetes are treated with IV insulin infusion lvhen plasma glucose levels exceed 180 to 200 mg/dl. Glucose goals are 140 to 180 mg/dl.

DON'T BE TRIGKED . DKA can present with abdominal pain. . Reducing the insulin infusion before complete clearing of ketones will cause a relapse of DKA. . Treatment of severe acidosis with bicarbonate is controversial, and evidence of benefit is lacking. Diabetes Care for Hospitalized Patients Treatment Insulin is the preferred treatment for achieving inpatient g$cemic control. Critically ill patients with type 2 diabetes are treated with IV insulin infusion lvhen plasma glucose levels exceed 180 to 200 mg/dl. Glucose goals are 140 to 180 mg/dl. For non critically ill patients who are eating, the insulin regimen should incorporate both basal and prandial coverage. Prandial coverage can be supplemented with correction factor insulin for preprandial hyperglycemia. DOil'? BE TRICKED . Do not select sliding scale insulin alone to treat in-hospital hyperglycemia. . Tight inpatient glycemic control (AO ffO mg/dl lq.+-O.t mmol/Ll) is not consistently associated with improved outcomes and may increase mortality. Continuing outpatient oral or noninsulin injectable agents is not recommended when patients are hospitalized because of the potential for hemodynamic or nutritional changes. Continuing oral agents should be considered only in a stable inpatient with glycemic control at goal who has no anticipated changes in nutrition or hemodynamic status. 52

Endocrinology and Metabolism Treatment Most patients with thyrotoxicosis benefit from B blockers to reduce adrenergic symptoms rapidly. Available treatment strategies for hyperthyroidism include antithyroid drugs, radioactive iodine therapy (r:rl), and thyroid surgery. Radioactive iodine . toxic multinodular goiter o toxic adenoma . Graves disease (usually following failed drug therapy) Radioactive iodine is not used during pregnancy or breastfeeding and may aggravate Graves ophthalmopathy. Moderate to severe Graves ophthalmopathy may require treatment with glucocorticoids, surgery or teprotumumab. Antithyroid drugs may lead to a drug-f ree remission ol Graves disease in up to 50'7, of patients after 2 years of treatment. STUDY TABLE: Comparison of Antithyroid Drugs Treatment lndicated for.. Watch for... Methimazole First-line antithyroid medication for most patients Agranulocytosis, drug rash, hepatotoxicity Propylth iou racil Treatment of choice in first trimester of pregnancy; Same as methimazole except more frequent preferred in thyroid storm (inhibits peripheralTa-T3 hepatotoxicity conversion) Thyroidectomy is preferred as definitive therapy fbr hyperthyroidism: r large goiter with compressive symptoms o intolerance to other therapies Subclinical hyperthyroidism is diagnosed by TSH suppression with normal T, and T3 levels. Treatment is recommended for TSH <0.1 pU/L and patients with symptoms. STUDY TABIE: Management of Thyrotoxicosis lf you see this.. Choose this... Sympathetic nervous Atenolol or propranolol system symptoms Severe Graves Methimazole or thyroidectomy ophthalmopathy Avoid radioactive iodine (may cause worsening of ophthalmopathy unless pretreated with g lucocorticoids)

STUDY TABIE: Management of Thyrotoxicosis lf you see this.. Choose this... Sympathetic nervous Atenolol or propranolol system symptoms Severe Graves Methimazole or thyroidectomy ophthalmopathy Avoid radioactive iodine (may cause worsening of ophthalmopathy unless pretreated with g lucocorticoids) Pregnancy Propylthiouracil in first trimester of pregnancy; methimazole thereafter Radioactive iodine is contraindicated Subclinical hyperthyroidism Methimazole if TSH <0.1 pU/mL Subacute thyroiditis NSAIDs or glucocorticoids for pain management, atenolol or propranolol for symptoms o{ hyperthyroidism, levothyroxine for symptomatic hypothyroidism, and periodic thyroid studies. ln 50% of patients, thyroid studies will normalize without intervention. Thyroid storm Propylthiouracil (preferred)or methimazole, iodine-potassium solutions, glucocorticoids, and B-blockers DON'T BE TRICKED . A fever or sore throat in a patient taking methimazole or propylthiouracil should be presumed to be agranulocytosis until proven otherwise. TESTYOURSELF An asymptomatic 78 year old woman has a serum TSH Ievel of 0.2 pU/mL. Serum T, and T1 levels are normal. ANSWER: For diagnosis, choose subclinical hyperthyroidism. For management, choose to repeat thyroid tests in 4 to 6 months. 60

Endocrinology and Metabolism Treatment Surgery is the treatment of choice. Use phenoxybenzamine to control BP preoperatively' Give IV normal saline to maintain intravascular volume; nitroprusside or phentolamine is indicated for treating intraoperative hypertensive crisis' DON'T BE TRICKED . For control of hypertension in patients with pheochromocytoma, select o-adrenergic blockers flrst' cl-Adrenergic blockade before adequate p-adrenergic blockade can result in severe paroxysmal hypertension. Primary Hypera ldosteronism Diagnosis Primary hyperaldosteronism is caused by aldosterone-producing adrenal adenomas (+0'1,) or by bilateral adrenal hyperplasia. Testing indications are: o untreated hypertension with sustained BP >150/100 mm Hg o resistant hypertension (>14o l9o mm Hg) with three drug therapy including a diuretic . hypertension and an incidentally discovered adrenal mass . hypertension associated with spontaneous or diuretic-induced hypokalemia . hypertension in the setting of a first degree relative with primary aldosteronism . hypertension in the setting of family history of hypertension onset <40 years of age Testing Evaluate patients using simultaneous measurements of plasma aldosterone and plasma renin activity. In patients taking an ACE inhibitor or an ARB, a nonsuppressed plasma renin level rules out mineralocorticoid excess. A plasma aldosterone-plasma renin activity ratio >20, with a plasma aldosterone level >15 ng/dl, strongly suggests primary hyperaldosteronism. The diagnosis is confirmed by demonstrating nonsuppressibility of elevated plasma aldosterone in response to a high salt load given intravenously or orally. Testing can be done in patients receiving treatment with all antihypertensive agents except spironolactone and eplerenone, both ofwhich antagonize the aldosterone receptor. After autonomous hyperaldosteronism is diagnosed, select CT of the adrenal glands. Adrenal vein sampling is needed before surgery to confirm the source of aldosterone secretion when imaging is unrevealing and to confirm lateralization when imaging demonstrates an adrenal adenoma. DOil'T BE TRICKED o A1most 507, of patients with hyperaldosteronism do NOT have hypokalemia

After autonomous hyperaldosteronism is diagnosed, select CT of the adrenal glands. Adrenal vein sampling is needed before surgery to confirm the source of aldosterone secretion when imaging is unrevealing and to confirm lateralization when imaging demonstrates an adrenal adenoma. DOil'T BE TRICKED o A1most 507, of patients with hyperaldosteronism do NOT have hypokalemia Treatment Spironolactone or eplerenone is the treatment ofchoice for adrenal hyperplasia. Laparoscopic adrenalectomy is indicated for an aldosterone-producing adenoma. 69

l Endocrinology and Metabolism l j I Primary Amenorrhea 1 1 I I l t Diagnosis I Primary amenorrhea is the failure of menstruation (never occurred). Approximately S07, of primary amenorrhea is caused by l chromosomal disorders, commonly Turner syndrome, in which part or all of an X chromosome is lost. 1 i Testing I Most important studies: o pregnancytest . karyotype . FSH, LH, TSH, prolactin level o pelvicultrasonography Secondary Amenorrhea Diagnosis Secondary amenorrhea is defined as absence of menses for more than 3 months in women who previously had regular men- strual cycles or 6 months in women who have irregular menses. History and physical examination include: . history of obstetric complications, which could lead to endometrial damage, scarring, or adhesions . stress, weight loss, significant exercise, eating disorders . newly initiated oral contraceptives, antipsychotics, or metoclopramide . symptoms of pituitary adenoma (secondary to mass effect or hyperfunction) . hirsutism, acne, history of PCOS Testing Test all women with secondary amenorrhea for pregnancy, the most common cause. In the absence of pregnancy, assess hormonal status with estradiol, FSH, LH, TSH, and prolactin levels. low estradiol and low or inappropriately normal FSH and LH indicate hypogonadotrophic hypogonadism. Causes include: o hypothyroidism . hyperprolaclinemia . hypothalamic (stress, weight loss, exercise) o pituitary (tumor, Sheehan syndrome) A progesterone challenge test is performed in these patients.

In the absence of pregnancy, assess hormonal status with estradiol, FSH, LH, TSH, and prolactin levels. low estradiol and low or inappropriately normal FSH and LH indicate hypogonadotrophic hypogonadism. Causes include: o hypothyroidism . hyperprolaclinemia . hypothalamic (stress, weight loss, exercise) o pituitary (tumor, Sheehan syndrome) A progesterone challenge test is performed in these patients. . No bleeding following a progesterone challenge indicates low estrogen because of hypothalamic hypogonadism; measure estradiol level to confirm. . Bleeding following progesterone challenge indicates a normal estrogen state and suggests possible hyperandrogenism (e.g., PCoS). 70

Endocrinology and Metabolism Low estradiol and elevated FSH and LH levels indicate hypergonadotrophic hypogonadism. Consider: o premature ovarian insufficiency (autoimmune) o chemotherapy o pelvic radiation Treatment Treat the underlying disorder. Prevent osteoporosis by choosing estrogen and progesterone replacement until menstruation returns to normal or age -50 years. For hypothalamic amenorrhea, choose reduced exercise, improved nutrition, and attention to emotional needs. Polycystic Ovary Synd rome Diagnosis PCOS is the most common cause of hirsutism with oligomenorrhea. Symptoms normally start at puberty or several years later and are slowly progressive. Diagnostic criteria differ but typically include at least two (or all) of the following: . ovulatory dysfunction (amenorrhea, oligomenorrhea, infertility) andior polycystic ovaries on ultrasound . laboratory or clinical evidence of hlperandrogenism (hirsutism, acne) o exclusion ofotherdisorders Testing Patients should be screened for diabetes, dyslipidemia, obesity, hypertension, and OSA. Serum testosterone and DHEAS should be measured in women with rapidly progressive hirsutism or virilization. DOil'T BE TRICKED . An androgen-secreting ovarian or adrenal tumor should be suspected in a woman with acute onset of rapidly progressive hirsutism or virilization. Treatment Weight loss is a first-line intervention. Choose metformin for prediabetes/diabetes. If fertility is not desired, choose oral contraceptive for treatment of hirsutism and regulation of menses; can add spironolactone if hirsutism remains a problem. If fertility is desired, ovulation can be induced with clomiphene citrate or letrozole. TESTYOURSELF A27-year oldwoman has had oligomenorrhea since age 14 years. She also has acanthosis nigricans and hirsutism but no galactor- rhea; she has obesity. She does not desire pregnancy. ANSWER: For diagnosis, choose PCOS. For management, choose intensive lifestyle modification and an oral contraceptive. 71

Endocrinology and Metabolism Treatment For severe, symptomatic hypercalcemia, select: . volume resuscitation with 0.9'1, saline o IV bisphosphonates . oral glucocorticoid therapy (if caused by multiple myeloma, B-cell lymphoma, or sarcoidosis) Parathyroidectomy is indicated for patients with primary hyperparathyroidism and hypercalcemic complications, such as kidney stones, bone disease, or previous episodes of hypercalcemic crisis. Asymptomatic patients are surgical candidates if they have any of the following: o serum calcium level >1 mg/dl above the upper limit of normal o creatinine clearance <60 mL/min . T score < 2.5 or vertebral lracture o age <50 years Watch for a precipitous fall in the serum calcium level caused by relative hypoparathyroidism after parathyroidectomy ("hungr) bone" syndrome). Monitor serum calcium after surgery and give oral calcium if mild hypocalcemia develops. Treat patients who are not candidates for parathyroidectomy with cinacalcet or bisphosphonates. DOil'T BE TRICKED . Loop diuretics are not recommended in the treatment of hypercalcemia unless kidney failure or HF is present, in which case, volume expansion should precede the administration of loop diuretics to avoid hypotension and further kidney injury. TEST YOURSETF A44-year old man has a 1-year history of fatigue and poor concentration. His serum calcium level is 10.9 mg/dl, serum phospho rus level is 2.8 mg/dl, and PTH level is 75 pg/ml. ANSWER: For diagnosis, choose primary hyperparathyroidism and measure serum vitamin D levels. For management, select parathyroidectomy. Multiple Endocrine Neoplasia Diagnosis STUDY TABLE: Multiple Endocrine Neoplasia Types 1 and 2 MENl MEN2 Multigland hyperparathyroidism is the most common Multigland hyperparathyroidism is the least common manifestation manifestation Pituitary neoplasms associated with prolactinoma (amenorrhea, Medullary thyroid cancer is the most common manifestation erectile dysfunction), acromegaly (enlargement of hands, feet, and may be associated with a palpable neck mass tongue; frontal bossing), Cushing disease (bruising, hypertension, centra I obesity, hi rsutism)

Multiple Endocrine Neoplasia Diagnosis STUDY TABLE: Multiple Endocrine Neoplasia Types 1 and 2 MENl MEN2 Multigland hyperparathyroidism is the most common Multigland hyperparathyroidism is the least common manifestation manifestation Pituitary neoplasms associated with prolactinoma (amenorrhea, Medullary thyroid cancer is the most common manifestation erectile dysfunction), acromegaly (enlargement of hands, feet, and may be associated with a palpable neck mass tongue; frontal bossing), Cushing disease (bruising, hypertension, centra I obesity, hi rsutism) Pancreatic NETs associated with gastrinoma (diarrhea, ulcers), Pheochromocytoma (hypertension, palpitations) insu linoma (fasting hypoglycemia), vasoactive intestinal ptide-secreting tumor (watery diarrhea, hypokalemia), id syndrome (diarrhea, flushing, right heart valvular lesion) 75

Endocrinology and Metabolism Treatment Treat acute symptomatic hypocalcemia with IV calcium gluconate and vitamin D. Chronic hylpocalcemia is treated with oral calcium supplements and vitamin D. Choose the [zpe of vitamin D based on the presence of underlying disease: . kidney disease: calcitriol (f ,ZS-dihydroxyvitamin D) . liver disease: 2S-hydroxycholecalci ferol . any other cause of hypocalcemia: cholecalciferol (Dr) or ergocalciferol (D) The main adverse effect of therapy is hypercalciuria and nephrolithiasis. Correct hypomagnesemia with magresium supplements. TESTYOURSETF A 46-year old woman has cramps in her hands and feet. She has pernicious anemia and Hashimoto thyroiditis. Her serum calcium level is 7.9 mg/dl, and her serum phosphorus level is 4.1 mg/dl. ANSWER: For diagnosis, choose autoimmune hypoparathyroidism and select a serum PTH level. Osteoporosis Screening The USPSTF recommends screening bone mineral density with DEXA in women >65 years and in postmenopausal women <65 years who are at increased risk as determined by a formal clinical risk assessment tool (e.g., FRAX). The American College of Rheumatologz recommends that patients anticipating receiving >3 months of glucocorticoid treatment should have bone mineral density testing within 6 months of starting glucocorticoid therapy, including: . all patients aged >40 years o patients aged <40 years with osteoporosis risk factors or a fragility fracture Screen men and women with risk factors for secondary osteoporosis (glucocorticoid use, hyperparathyroidism, ADT [men], malabsorption). DOil'T BE TRICKED o Do not repeat annual DEXA in women with normal DEXA results without risk factors. The optimal screening interval is unknown. Diagnosis Osteoporosis is characterized by an increased predisposition to fractures. . DEXA T score of -1.0 to -2.4 defines osteopenia. o DEXA T-score of <-2.5 defines osteoporosis. o Osteoporosis is also diagnosed by a history offragility fracture (fracture from a fall at standing height or lower) Causes The most common cause of osteoporosis in women is estrogen deflciency and in men is testosterone deflciency Secondary causes include:

. DEXA T score of -1.0 to -2.4 defines osteopenia. o DEXA T-score of <-2.5 defines osteoporosis. o Osteoporosis is also diagnosed by a history offragility fracture (fracture from a fall at standing height or lower) Causes The most common cause of osteoporosis in women is estrogen deflciency and in men is testosterone deflciency Secondary causes include: . hyperthyroidism, hyperparathyroidism, Cushing syndrome . malabsorption (Crohn disease, intestinal resection, celiac disease) 77

Endocrinology and Metabolism Treatment Indications to treat Paget disease include bone pain, radiculopa thy, or involvement of a weight bearing bone or joint regardless of symptoms. Treatment is ffpically a one-time dose of IV zole dronic acid. 'tiii. Paget Disease: X-ray showing "cotton wool" appearance of the skull typical of Paget disease. 81

Gastroenterology and Hepatology Treatment Liver transplantation is the only effective treatment. TEST YOURSELF A 4S-year-old man with a 15 year history of ulcerative colitis develops fatigue and pruritus. Serum alkaline phosphatase level is 75oUlL, AST is 48 U/L, ALI is 60 U/L, and total bilirubin is 2.0 mg/dl. ANSWER: For diagnosis, choose PSC. For management, select MRCP and colonoscopy for colorectal cancer screening. Cirrhosis Diagnosis Patients with complications of cirrhosis (hepatic encephalopathy, variceal hemorrhage, ascites, spontaneous bacterial peritoni- tis, hepatorenal syndrome, jaundice, or HCC) have decompensated cirrhosis. Portal hypertension can be divided into prehepatic, intrahepatic, and posthepatic causes. The most common cause of portal hypertension is cirrhosis, an intrahepatic form. Examples of pre- and posthepatic portal hypertension are portal vein thrombo- sis and Budd Chiari syndrome, respectively. Complications ofportal hypertension include gastroesophageal varices, ascites, and spontaneous bacterial peritonitis. SIUDY TABLE: Syndromes Associated With Cirrhosis Syndrome Comments Hepatic encephalopathy Neuropsychiatric syndrome with symptoms ranging from mild cognitive changes to coma Measuring plasma ammonia level can be helpful Sometimes precipitated by infection, volume depletion, Gl bleeding, or sedating medications Hepatopulmonary syndrome Dyspnea, hypoxemia, increased A-a gradient; may exhibit platypnea (increased dyspnea sitting up and decreased dyspnea lying flat) Confirm using transthoracic contrast echocardiography Portopu I mona ry hypertension Pulmonary hypertension with portal hypertension Patients should undergo echocardiography

SIUDY TABLE: Syndromes Associated With Cirrhosis Syndrome Comments Hepatic encephalopathy Neuropsychiatric syndrome with symptoms ranging from mild cognitive changes to coma Measuring plasma ammonia level can be helpful Sometimes precipitated by infection, volume depletion, Gl bleeding, or sedating medications Hepatopulmonary syndrome Dyspnea, hypoxemia, increased A-a gradient; may exhibit platypnea (increased dyspnea sitting up and decreased dyspnea lying flat) Confirm using transthoracic contrast echocardiography Portopu I mona ry hypertension Pulmonary hypertension with portal hypertension Patients should undergo echocardiography RV systolic pressure >50 mm Hg requires investigation for causes of pulmonary hypertension Some patients may benefit from liver transplantation Hepatorenal syndrome type 1 lncrease in serum creatinine of at least 0.3 mg/dL and /or >50"/ofrom baseline within 48 hours, bland urinalysis, and normalfindings on kidney ultrasonography Lack of improvement in kidney function after withdrawal of diuretics and 2 days of volume expansion with intravenous albumin Low urine sodium, low fractional excretion of sodium, and oliguria Hepatorenal syndrome type 2 Less severe, with a more gradual decline in kidneyfunction and association with diuretic-refractory ascites Hepatic osteodystrophy Encompasses osteoporosis, osteopenia, and rarely osteomalacia in the context of liver disease Standard evaluation includes calcium, phosphate, and vitamin D levels; DEXA scanning is recommended for patients with cirrhosis or primary biliary cholangitis and before liver transplantation Osteoporosis should be managed with a bisphosphonate (after vitamin D repletion) 106

Gastroenterology and Hepatology Treatment For patients with acute liver failure, choose: . immediate contact with liver transplantation center . Ai acetylcysteine for confirmed or suspected acetaminophen poisoning . Iactulose for any degree of encephalopathy DOil'T BE TRICKED . Head CT should be performed in patients with acute liver failure and altered mental status to rule out cerebral edema or intracranial hemorrhage. Kayser.Fleisrher Ring: A Kayser-Fleischer ring in TESTYOURSELF the cornea is bracketed wilh arrowheads. A 24 year-old man has a l-week history ofnausea, jaundice, fatigue, and recent confu- sion. The INR is 2.3, serum AST is 940 U/L, and total bilirubin is 12.6 mg/dl. HBsAg and IgM anti-HBc are both positive. ANSWER: For diagnosis, choose acute liver failure secondary to acute HBV infection. For management, contact liver transplantation center. Liver Disease Associated With Pregnancy Several liver diseases are uniquely seen in pregnancy; they are outlined in the table below.

Kayser.Fleisrher Ring: A Kayser-Fleischer ring in TESTYOURSELF the cornea is bracketed wilh arrowheads. A 24 year-old man has a l-week history ofnausea, jaundice, fatigue, and recent confu- sion. The INR is 2.3, serum AST is 940 U/L, and total bilirubin is 12.6 mg/dl. HBsAg and IgM anti-HBc are both positive. ANSWER: For diagnosis, choose acute liver failure secondary to acute HBV infection. For management, contact liver transplantation center. Liver Disease Associated With Pregnancy Several liver diseases are uniquely seen in pregnancy; they are outlined in the table below. STUOY TABLE: Liver Diseases Unique to Pregnancy Disease Trimester Clinical Features Laboratory Studies Bilirubin Level Management Hyperemesis 1st Severe vomiting ALT elevated in 50% Normal Hydration, pyridoxine, gravidarum of patients, may be antiemetics 20x ULN lntrahepatic 2nd or 3rd Pruritus, often intense ALT normalto 10x Normalto mildly Ursodeoxycholic acid cholestasis o{ ULN, elevated serum elevated pregnancy bile acids, alkaline phosphatase Preeclampsia 3rd Hypertension, Mild increase in ALT Normal Delivery edema, and proteinuria HELLP syndrome 3rd Features of Hemolysis, elevated Usually normal Delivery preeclampsia, ALT, thrombocytopenia abdominal pain, nausea

STUOY TABLE: Liver Diseases Unique to Pregnancy Disease Trimester Clinical Features Laboratory Studies Bilirubin Level Management Hyperemesis 1st Severe vomiting ALT elevated in 50% Normal Hydration, pyridoxine, gravidarum of patients, may be antiemetics 20x ULN lntrahepatic 2nd or 3rd Pruritus, often intense ALT normalto 10x Normalto mildly Ursodeoxycholic acid cholestasis o{ ULN, elevated serum elevated pregnancy bile acids, alkaline phosphatase Preeclampsia 3rd Hypertension, Mild increase in ALT Normal Delivery edema, and proteinuria HELLP syndrome 3rd Features of Hemolysis, elevated Usually normal Delivery preeclampsia, ALT, thrombocytopenia abdominal pain, nausea AFLP 3rd Features of Hemolysis, elevated Normal unless Delivery preeclampsia, ALl, th rom bocytopenia, severe abdominal pain, hypoglycemia, nausea prolonged INR DON'T BE TRICKED o HELLP syndrome dilTers from AFLP in that HELLP syndrome is more closely associated with microangiopathic hemolytic anemia and AFLP is more associated with encephalopathy and coagulation abnormalities. 109

General lnternal Medicine Treatment First-line therapy includes compression (stockings, wraps, pumps) and leg elevation. Emollients are used for dry itchy skin; topical glucocorticoids can be added lor eczema. In addition to compression, patients with venous ulcers require debridement ol devitalized tissue and simple nonadherent dressings. Antibiotics are limited to patients with suspected infection (increased pain, drainage, surrounding cellulitis). DON'T BE TRICKED . Loop diuretic therapy is not recommended as flrst-line therapy for edema from chronic venous insufficiency Syncope Diagnosis Syncope can be classified as neurally mediated (reflex), cardiovascular, orthostatic, neurologic, psychogenic, or idiopathic. Neurally mediated syncope is the most common type and is seen primarily in younger adults. Neurally mediated syncope includes vasovagal syncope, situational syncope, and carotid sinus hypersensitivity. Vasovagal syncope is the most common form ofl neurally mediated syncope and can be diagnosed by historical characteristics and the absence of any suggestion of heart disease from the physical examination and ECG. Look for the 4 P's: o previous history . posture (prolonged standing) . provoking factors (blood draw pain, emotion) . prodromal symptoms (sweating, nausea, feeling warm) A history ofheart disease, chest pain before syncope, significant cardiac risk factors, significant injury during syncope, or exer tional syncope suggests structural cardiac disease or arrhythmias as the cause of syncope.

o previous history . posture (prolonged standing) . provoking factors (blood draw pain, emotion) . prodromal symptoms (sweating, nausea, feeling warm) A history ofheart disease, chest pain before syncope, significant cardiac risk factors, significant injury during syncope, or exer tional syncope suggests structural cardiac disease or arrhythmias as the cause of syncope. STUDY TABLE: Causes of Syncope lf you see this... Diagnose this... A prodrome of nausea, diaphoresis, pallor, and Vasovagal syncope brief loss of consciousness (<1 min)with rapid recovery and absence of postsyncopal confusion Preceding pressure on the carotid sinus (tight Carotid sinus hypersensitivity collar, sudden turning of head) Association with specific activities (urination, Situational syncope coug h, swallowing, defecation) On assuming an upright position Orthostatic hypotension caused by hypovolemia, pharmacologic agents, or autonomic neryous system disorders (e.9., parkinsonism, diabetes) Brainstem neurologic signs and symptoms Posterior circulation vascular disease; consider subclavian steal syndrome if preceded by upper extremity exercise Witnessed "seizure" Syncope may cause tonic-clonic jerking of extremities; primary seizure is unlikely if findings of diaphoresis or nausea before the event, a brief episode of unconsciousness, and immediate postsyncopal orientation are present Related to exercise or associated with angina Obstruction to LV outflow: AS, HCM; also PE and PH Syncope with sudden onset without prodrome Arrhythmia, sinoatrial and AV node dysfunction (ischemic heart disease and associated with use of B-blockers, calcium channel blockers, and antiarrhythmic d rugs) Syncope following a meal Postprandial syncope, often in older adult patients

STUDY TABLE: Causes of Syncope lf you see this... Diagnose this... A prodrome of nausea, diaphoresis, pallor, and Vasovagal syncope brief loss of consciousness (<1 min)with rapid recovery and absence of postsyncopal confusion Preceding pressure on the carotid sinus (tight Carotid sinus hypersensitivity collar, sudden turning of head) Association with specific activities (urination, Situational syncope coug h, swallowing, defecation) On assuming an upright position Orthostatic hypotension caused by hypovolemia, pharmacologic agents, or autonomic neryous system disorders (e.9., parkinsonism, diabetes) Brainstem neurologic signs and symptoms Posterior circulation vascular disease; consider subclavian steal syndrome if preceded by upper extremity exercise Witnessed "seizure" Syncope may cause tonic-clonic jerking of extremities; primary seizure is unlikely if findings of diaphoresis or nausea before the event, a brief episode of unconsciousness, and immediate postsyncopal orientation are present Related to exercise or associated with angina Obstruction to LV outflow: AS, HCM; also PE and PH Syncope with sudden onset without prodrome Arrhythmia, sinoatrial and AV node dysfunction (ischemic heart disease and associated with use of B-blockers, calcium channel blockers, and antiarrhythmic d rugs) Syncope following a meal Postprandial syncope, often in older adult patients Patients with uncomplicated vasovagal faint can be discharged home without additional evaluation. Patients with suspected cardiac causes of syncope should be hospitalized. 122

General lnternal Medicine Treatment Lithium is the most effective mood stabilizer, but Iong term therapy carries significant side effects, including kidney disease, hypothyroidism, and DI. Anticon'uulsants and second generation antipsychotics are alternative first-line treatments. Monotherapy with SSRIs may unmask mania in patients with untreated bipolar disorder. TESTYOURSELF A 27-year-old woman requests thyroid medication to make her "stronger" because she wants to run for the senatorial position for the state of California. She is sleeping 2 to 3 hours per night and has not been eating. She spends her time writing her political action plan and shopping and has exceeded the limit on her credit card. ANSWER: For diagnosis, choose mania. Generalized Anxiety Disorder Diagnosis Generalized anxiety disorder is characterized by pervasive and excessive anxiety about a variety ofevents or activities, restless- ness, difficulty concentrating, irritability, functional impairment, and sleep disturbance. Patients commonly have a comorbid psychiatric disorder. Treatment CBT, with or without pharmacologic therapy, is flrst-line treatment for generalized anxiety disorder. SSRIs and SNRIs are effec- tive. Benzodiazepines are acceptable for short-term use while titrating antidepressant doses, but dependence and tolerance complicate long term use. Benzodiazepines should be avoided in patients with a history of substance use disorder. Social Anxiety Disorder Diagnosis Diagnostic criteria for social anxiety disorder include severe fear of social or performance situations resulting in symptoms such as blushing, dyspnea, palpitations, and emotional distress. Anxiety may be generalized or specific to a single activity. Treatment Treat social anxiety disorder with CBT, SSRIs, and SNRIs. Panic Disorder Diagnosis Panic attacks are characterized by sudden onset and rapid escalation of extreme fear or anxiety along with at least four of the following: o fearofdying o fear oflosing control . palpitations, diaphoresis, tremor, dyspnea, choking sensation 134

General lnternal Medicine r chest pain, nausea, dizziness, chills or heat sensations o paresthesia o derealization (perception that the world is not real) Panic disorder involves recurrent, unexpected panic attacks and persistent worry about future attacks. Treatment CBT and SSRIs or SNRIs are first-line treatment. Long-acting benzodiazepines can be used as short-term therapy for disabling disorders until first-line treatments become effective. DOil'T BE TRICKED o Do not prescribe benzodiazepines as either first-line or long-term treatment for panic disorder Posttra u matic Stress Disorder Diagnosis Indicators suggesting PTSD include: 1. history of exposure to trauma 2. persistent re-experiencing of the traumatic event 3. avoidance of stimuli associated with the trauma 4. increased arousal Assess for coexisting psychiatric disorders and domestic abuse. Treatment CBT is the treatment ofchoice for PTSD. Sertraline, paroxetine, venlafaxine, and nefazodone are adjuvant treatments. DON'T BETRICKED o Do not prescribe benzodiazepines for PTSD. Obsessive-Com pu lsive Disorder Diagnosis Obsessions are defined as persistent ideas, thoughts, impulses, or images that are intrusive and inappropriate and associated with significant anxiety or distress. Compulsions are repetitive behaviors (handwashing, checking, and ordering) or mental acts (counting or repeating words silently) performed to try to decrease the anxiety or stress associated with the obsessions. The person must recognize that the obsessions or compulsions are excessive or unreasonable. Treatment Obsessive-compulsive disorder is treated with CBT and often with an SSRI. 135

General lnternal Medicine Treatment Advanced static mattresses and overlays help prevent pressure injuries in at risk persons. STUDY TABLE: Pressure lnjury Staging and Therapy Ulcer Stage Therapy Stage 1:The skin is intact with nonblanchable redness For all stages: positioning and support to minimize tissue pressure Stage 2: Shallow ulcer with a red-pink wound bed or serum-filled Occlusive or semipermeable dressing that will maintain a moist blister wound environment (e.9., hydrocolloid) Stage 3: Subcutaneous fat may be visible Pain control, assessment for nutritional de{iciencies, debridement, topical or systemic antibiotics Stage 4: Exposed bone, tendon, or muscle Same as stage 3 Unstageable: Full-thickness tissue loss in which the base of the Remove eschal then stage ulcer is covered by slough or eschar Basic rules for treating pressure injuries . Pressureredistribution . Pressure reducing surface (e.g., advanced mattresses and overlays) o Dressings should maintain a moist wound environment and manage exudates. o Restrict systemic antibiotics for cellulitis treatment (surrounding erythema, warmth, pain) r Debride eschars and nonviable tissue. DON'T BETRICKED . Nutritional supplementation to enhance wound healing remains controversial. . Hydrotherapy and hyperbaric oxygen therapies are not effective in the treatment ofpressure injuries. o Always consider the possibility of underlying osteomyelitis. Dermatolog ic Conditions of Aging Excessive dry skin (xerosis) may cause xerotic dermatitis. When severe, lesions are erythematous with plate like cracked scale. Aging is the most common cause. Treatment includes a short term, medium-potency topical glucocorticoid ointment base and chronic use of emollients. Xerotic Dermatitis: Xerotic dermatitis is characterized by redness and a "tile-like" pattern on dry skin (xerosis) with evidence ol trauma because of scratching.

Xerotic Dermatitis: Xerotic dermatitis is characterized by redness and a "tile-like" pattern on dry skin (xerosis) with evidence ol trauma because of scratching. Actinic purpura appears as purpuric macules or patches, most commonly on the forearms, due to minor trauma. No testing needs to be performed. There is no treatment for actinic purpura, but sun protection is recom mended to prevent further damage. Attinit Purpun: Actinic purpura appears as purpuric macules or patches. 142

General lnternal Medicine Solar lentigines are tan or light brown, 1 to 3 cm well defined macules on sun-exposed areas of older adults. They are a marker of sun damage. When solar lentigines are larger than 1 cm or irregular in shape, melanoma is in the differential diagnosis, and biopsy should be considered. Solar Lentlgines: Solar lentigines (solar lentigo) are brown macules and patches that occur in oldel fair-skinned persons in sun-damaged areas.

Solar lentigines are tan or light brown, 1 to 3 cm well defined macules on sun-exposed areas of older adults. They are a marker of sun damage. When solar lentigines are larger than 1 cm or irregular in shape, melanoma is in the differential diagnosis, and biopsy should be considered. Solar Lentlgines: Solar lentigines (solar lentigo) are brown macules and patches that occur in oldel fair-skinned persons in sun-damaged areas. Screening and Prevention STUDY fABLE: Summary of Vaccination Recommendations for Adults 19 Years or Older Disease Vaccine Type ACIP Recommendation lnfluenza lnactivated, recombinant One dose annually, including pregnant women and those with HIV trivalent or quadrivalent infection Tetanus, diphtheria, and lnactivated One dose of Tdap (if not previously administered); Td orTdap booster pertu ssis every 1 0 years for all adults; one dose Tdap each pregnancy between 27 to 36 weeks'gestation Varicella Live attenuated For all immunocompetent persons lacking immunity Herpes zoster Recombinant All nonimmunocompromised persons aged )50 y, including those previously vaccinated with the inactivated vaccine or with previous herpes zoster infection Pneumococcal lnactivated See Study Table: Pneumococcal lmmunization HPV lnactivated Ages 19-26 y Ages27-45 y based on shared clinical decision-making MMR Live attenuated Adults born in 1957 or later without evidence of vaccination or immunity Meningococcal (MenACWY) lnactivated All adolescents aged 11-12 y, with a booster dose at age 1 6 years (catch- up boostervaccination age 19-21 y) Meningococcal (MenB) lnactivated Ages 16-23 y on basis of shared clinical decision-making" Hepatitis A lnactivated Any adult requesting immunization and those at high risk Hepatitis B lnactivated Any adult requesting immunization and those at high risk ACIP = Advisory Committee on lmmunization Practices.

Screening and Prevention STUDY fABLE: Summary of Vaccination Recommendations for Adults 19 Years or Older Disease Vaccine Type ACIP Recommendation lnfluenza lnactivated, recombinant One dose annually, including pregnant women and those with HIV trivalent or quadrivalent infection Tetanus, diphtheria, and lnactivated One dose of Tdap (if not previously administered); Td orTdap booster pertu ssis every 1 0 years for all adults; one dose Tdap each pregnancy between 27 to 36 weeks'gestation Varicella Live attenuated For all immunocompetent persons lacking immunity Herpes zoster Recombinant All nonimmunocompromised persons aged )50 y, including those previously vaccinated with the inactivated vaccine or with previous herpes zoster infection Pneumococcal lnactivated See Study Table: Pneumococcal lmmunization HPV lnactivated Ages 19-26 y Ages27-45 y based on shared clinical decision-making MMR Live attenuated Adults born in 1957 or later without evidence of vaccination or immunity Meningococcal (MenACWY) lnactivated All adolescents aged 11-12 y, with a booster dose at age 1 6 years (catch- up boostervaccination age 19-21 y) Meningococcal (MenB) lnactivated Ages 16-23 y on basis of shared clinical decision-making" Hepatitis A lnactivated Any adult requesting immunization and those at high risk Hepatitis B lnactivated Any adult requesting immunization and those at high risk ACIP = Advisory Committee on lmmunization Practices. "See Study Table: Meningococcal Vaccines for Persons at lncreased Risk of Meningococcal Disease.

Screening and Prevention STUDY fABLE: Summary of Vaccination Recommendations for Adults 19 Years or Older Disease Vaccine Type ACIP Recommendation lnfluenza lnactivated, recombinant One dose annually, including pregnant women and those with HIV trivalent or quadrivalent infection Tetanus, diphtheria, and lnactivated One dose of Tdap (if not previously administered); Td orTdap booster pertu ssis every 1 0 years for all adults; one dose Tdap each pregnancy between 27 to 36 weeks'gestation Varicella Live attenuated For all immunocompetent persons lacking immunity Herpes zoster Recombinant All nonimmunocompromised persons aged )50 y, including those previously vaccinated with the inactivated vaccine or with previous herpes zoster infection Pneumococcal lnactivated See Study Table: Pneumococcal lmmunization HPV lnactivated Ages 19-26 y Ages27-45 y based on shared clinical decision-making MMR Live attenuated Adults born in 1957 or later without evidence of vaccination or immunity Meningococcal (MenACWY) lnactivated All adolescents aged 11-12 y, with a booster dose at age 1 6 years (catch- up boostervaccination age 19-21 y) Meningococcal (MenB) lnactivated Ages 16-23 y on basis of shared clinical decision-making" Hepatitis A lnactivated Any adult requesting immunization and those at high risk Hepatitis B lnactivated Any adult requesting immunization and those at high risk ACIP = Advisory Committee on lmmunization Practices. "See Study Table: Meningococcal Vaccines for Persons at lncreased Risk of Meningococcal Disease. DON'T BE TRICKED . For pregnant women, do not select live vaccines, including MMR, intranasal influenza, yellow fever, and varicella; delay recombinant zoster vaccine until after pregnancy. . All available influenza vaccines are safe in egg-allergic patients.

"See Study Table: Meningococcal Vaccines for Persons at lncreased Risk of Meningococcal Disease. DON'T BE TRICKED . For pregnant women, do not select live vaccines, including MMR, intranasal influenza, yellow fever, and varicella; delay recombinant zoster vaccine until after pregnancy. . All available influenza vaccines are safe in egg-allergic patients. 143

General lnternal Medicine Treatment Treatment options include lifestyle modification, pharmacotherapy, and bariatric surgery. A reasonable initial goal is weight loss of 0.5 kg to 1.0 kg/week (l.l 2.2lb) to achieve a total weight loss of l0%. A specific daily calorie limit should be prescribed (typically, 1500-1800 kcal/d for men and 1200-1500 kcal/d for women). All diets are equally effective. Exercise >150 min/week is helpful as an adjunct to diet change but not effective as monotherapy. Pharmacologic therapy may be used as adjunctive therapy in patients with a BMI >30 or in patients with a BMI >27 and weight- associated comorbidities. STUtrY tAB[E: Drugs for Weight Loss Drug Expected Cautions and Contraindications Weight Loss Orlistat (inhibitor of gastric and pancreatic lipases); lowest 3kg Diarrhea, oily stools; must replace fat-soluble vitamins risk of patient discontinuation Combination phentermine (sympathomimetic) and Iow- 8-1 0 ks Contraindications: pregnancy, glaucoma, dose topiramate (anticonvulsant) hyperthyroidism, and MAOI use Combination sustained-release bupropion 2-6kg Contraindications: epilepsy, uncontrolled hypertension, ( nore p nep h ri n e-d o pa m i n e reu pta ke i n h i bito r) a n d i and opioid or opioid agonist use sustained-release naltrexone (opioid receptor antagonist) Liraglutide 5.3 kg Gastrointestinal upset, headache, nasopharyngitis Bariatric surgery is considered for patients with a BMI >40 and for patients with a BMI >35 with serious obesity-related comor- bidities (severe sleep apnea, diabetes, severe joint disease). Bariatric surgery outcomes are associated with . improved control or remission of type 2 diabetes o improved quality of life . reduced medication use . reduced mortality Commonly performed bariatric procedures include Iaparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, and sleeve gastrectomy.

Bariatric surgery outcomes are associated with . improved control or remission of type 2 diabetes o improved quality of life . reduced medication use . reduced mortality Commonly performed bariatric procedures include Iaparoscopic adjustable gastric banding, Roux-en-Y gastric bypass, and sleeve gastrectomy. 5?UDY TABLE: Bariatric Surgery Complications Surgery Complications Banding procedures lntractable nausea and vomiting Marginal ulcers, stomal obstruction Gastric bypass Stomal stenosis Cholelithiasis Nephrolithiasis Dumping syndrome Anatomic stricture or ulceration Bacterial overgrowth Micronutrient deficiencies: folate; vitamins 81,86,BD, C, A, D, E, and K; iron; zinc; selenium; and copper Sleeve gastrectomy Staple-line bleeding, stenosis (dysphagia and vomiting), and staple-line leakage TESTYOURSEIF A 41 year old woman is evaluated for persistent nausea and vomiting after laparoscopic gastric bypass surgery 6 weeks ago for morbid obesity. ANSWER: For management, select upper endoscopy to diagnose stomal stenosis or marginal ulcer. 151

General lnternal Medicine Treatment Treat otitis or cerumen impaction if present. Select urgent referral to an ENT specialist for sudden, unexplained hearing loss. The evidence for treatment with glucocorticoids is weak but frequently provided. For presbycusis, hearing aids that amplify sound are often helpful. TESTYOURSELF A 35 year old previously healthy man has had difficutfy hearing in his right ear since last night. He has rhinorrhea and nasal con gestion. His external auditory canals and tympanic membranes are normal; a 512-Hz tuning fork is placed on his fbrehead. and he hears the tone louder in his left ear than in his right ear. ANSWER: For diagnosis, choose sudden sensorineural hearing loss. For management, select emergent ENT referral. Otitis Media Diagnosis Acute otitis media is characterized by fluid and inflammation in the middle ear accompanied by symptoms of infection. M:rny patients first present with viral URI symptoms. Otitis media lvith effusion is characterized by fluid in the middle ear without signs of infection. Treatment Evidence on treatment in adults is lacking. However, analgesic therapy, antibiotics, and decongestants are the mainstays of treat ment. No evidence favors one antibiotic over another; amoxicillin or amoxicillin clavulanic acid provides coverage lor the most common organisms. Complications include hearing loss. tympanic membrane perfbration. meningitis, and mastoiditis. External Otitis Diagnosis Patients with typical external otitis present with otalgia, ear dis charge. pruritus. and conductive hearing loss. Be aware ofother varieties of external otitis: o Malignant external otitis is characterized by systemic toxic ity and evidence of infection spread beyond the ear canal (mastoid bone, cellulitis) and is typically found in older adult patients with type 2 diabetes or patients who are immunocompromised. It is most commonly caused by Pse udomo nas ae ruginosa. o Ramsay Hunt syndrome is caused by varicella zoster viral infection and characterized by facial nerve paralysis. senso rineural hearing loss, and vesicular lesions on and in the ear canal. Ramsay Hunt Syndrome: Ihese vesicular lesions on and in the ear canal are characteristic of Ramsay Hunt syndrome caused by VZV infection. 155

General lnternal Medicine Treatment Therapy is not required. A shave excision or liquid nitrogen destruction can be performed for lesions that are irritated (e.g., rubbed by clothing or jewelry). DOil'T BE TRICKED . Rapid onset of multiple pruritic seborrheic keratoses can be a sign of GI adenocarcinoma. Warts, Calluses, Corns, and Skin Tags Seborrheic l(eratoses: Brown to tan, sharply demarcated, waxy-like papules, plaques, and nodules are characteristic o{ seborrheic keratoses. Diagnosis Warts: Look for flesh-colored, exophytic, hyperkeratotic papules or nodules. Anogenital warts (condyloma acuminata) present as single or multiple papules on the penis, vulva, or perianal area and may be flat topped or cauliflower-like papules. Calluses and corns: A callus is a collection of thickened, hardened stratum corneum that presents as a flat papule or plaque at the site of repetitive trauma, frequently over bones. Corns have more distinct edges, are more rounded, and are typically seen on the sides or tops oftoes. Skin tags: Skin-colored, pedunculated papules. They are most commonly seen on the neck and skin folds in older adults and those with obesity and diabetes. Treatment HPV vaccination is recommended for young persons to prevent cervical and anal carcinoma and should also serve to decrease anogenital warts. Warts are usually self limited, and treatment is not necessary except for protracted courses or in immunocompromised patients. Treat common warts with salicylic acid (a keratolytic agent). Alternatives to drug therapy include cryotherapy. Podophyllin is often used as the initial therapy for anogenital warts. Corns are treated with mechanical or chemical paring with salicylic acid, but removing the pressure from the site is necessary to prevent reformation. If skin tags become necrotic or crusted, they may require removal with cryotherapy or snip excision. Dysplastic Nevi Diagnosis Dysplastic nevi have some features of melanoma, including: o diameter >5 mm . asymmetric shape with indistinct borders . a "fried egg" appearance with a darker, elevated central portion and tan, flat shoulders blending into the surrounding skin o pigmentation ranging from light tan to dark brown and occasionally black 183

Hematology Treatment Treat the underlying condition resulting in normocltic anemia. Anemia of inflammation is usually not severe and rarely requires therapy beyond the underlying condition. Microcytic Anemia Microcy.tic anemia is associated with an MCV of <80 fL. The most common cause of microcytic anemia is iron deficiency, usually related to menstrual or GI blood loss or malabsorption syndromes (celiac disease). Other causes include inflammatory disorders and lead intoxication' Patients with microcl'tic ane- mia since childhood should be evaluated for the thalassemia trait, other hemoglobinopathies (thalassemia), or ineffective erythropoiesis (hereditary sideroblastic anemia). lron Deficiency Anemia Diagnosis: The hallmark of iron deficiency is a microcytic hypochromic anemia. Signs and symptoms of iron deficiency include pica, restless legs syndrome, hair loss, spoon nails (koilo- nychia), and conjunctival rim pallor. As hemoglobin levels decline, erythrocytes become heterogene- ous in size (anisocytosis) and shape (poikilocltosis). An elevated platelet count (usually not >1 million/pl) may be found in early disease. restins ;:tiitflI;;i"[i'Jl;;Il;lxtffiiiffltj:tTlii]:lx]:Ji:i:xlx Diagnosticstudies: rioraspect lnothenrtrisehealthypatients,theanteriorconjunctivalrimisredder' . serum iron and ferritin levels and TIBC . hemoglobin electrophoresis if iron studies are normal o bidirectional endoscopy studies, starting with colonoscopy, if iron deflciency is present in men or postmenopausal women Serum ferritin levels are the most useful test in the diagnosis of iron deficiency. However, because ferritin is an acute-phase reactant, it has less diagnostic value in patients with infection or inflammatory disorders. Virtually all patients with serum ferritin levels <14 ng/ml are iron deflcient. Treatment The least expensive oral iron replacement, iron sulfate, is as effective as any of the more expensive oral preparations. Oral iron once daily or every other day for 6 months is the standard treatment. Parenteral iron preparations are indicated only for patients who cannot tolerate or absorb oral iron or who are receiving hemodialysis. Transfusion is reserved for severely symptomatic anemia. 202

I Hematology DOI{'T BE TRICKED o In iron deflciency, abnormalities in iron studies typically occur first, followed by anemia and then morphologic changes in the cell. TEST YOURSETF A 20 year old woman with iron deficiency anemia does not respond to oral iron therapy. Review of systems is remarkable for IBS. ANSWER: For diagnosis, test for celiac disease. Mictocytic Anemia: The eryth rocytes show hypoch rom ia, a n isocytosis, a nd poi ki l- Macrocytic Anemia ocytosis. Erythrocytes in thalassemia have less variability in size and shape, and target cells are seen. Diagnosis Macrocytic anemia is associated with an MCV >100 fL. Macro ovalocytes and hypersegmented neutrophils (>s lobes) may also be present. Causes include: . fblate and/or cobalamin deficiencies . drugs affecting folate metabolism and/or DNA synthesis (alcohol, hydroxyurea, methotrexate) . acquired causes of megaloblastic maturation such as MDS Anemia associated with an MCV >115 fL is almost always a result of megaloblastic disorders. Because megaloblastic causes of anemia affect trilineage hematopoiesis, Ieukopenia and thrombocytopenia may accompany anemia. Macrocytic anemia may also be caused by nonmegaloblastic disorders.

. fblate and/or cobalamin deficiencies . drugs affecting folate metabolism and/or DNA synthesis (alcohol, hydroxyurea, methotrexate) . acquired causes of megaloblastic maturation such as MDS Anemia associated with an MCV >115 fL is almost always a result of megaloblastic disorders. Because megaloblastic causes of anemia affect trilineage hematopoiesis, Ieukopenia and thrombocytopenia may accompany anemia. Macrocytic anemia may also be caused by nonmegaloblastic disorders. . Large target cells (MCV 105-110 fL) and acanthocytes (spur '\w@ fl\ cells with a small number of spicules of variable size and distribution on the cell surface) signiff membrane changes associated with liver disease. fr 'q.,*Y f* e\*#g \""'f o Diminished splenic function (hyposplenism or asplenia) h ,*I results in large target cells, acanthocytes, Howell-Jolly ,y bodies, and variable numbers of nucleated erythroc).tes. ffi t a Testing If serum vitamin B,, levels are borderline low (ZOO 300 pg/ml), measure serum methylmalonic acid and homocysteine levels. Elevated levels confirm vitamin B,, deficiency; elevated homo cysteine and normal methylmalonic acid levels are associated Hypersegmented Polymorphonuclear Cell: The erythrocytes are large ovalo- with folate deficiency. cytes, and a single PMN cell has more than five nuclear lobes. Consider vitamin 812 or folate deficiency (megaloblastic anemia).

Testing If serum vitamin B,, levels are borderline low (ZOO 300 pg/ml), measure serum methylmalonic acid and homocysteine levels. Elevated levels confirm vitamin B,, deficiency; elevated homo cysteine and normal methylmalonic acid levels are associated Hypersegmented Polymorphonuclear Cell: The erythrocytes are large ovalo- with folate deficiency. cytes, and a single PMN cell has more than five nuclear lobes. Consider vitamin 812 or folate deficiency (megaloblastic anemia). Treatment High dose oral vitamin B,, supplementation of 1000 to 2000 pg/d is usually as effective as parenteral administration and should be the initial therapy for most patients. 203

Hematology l Patients with severe anemia, neurologic dysfunction, or those not responding to oral replacement may require parenteral B,, injections. Malabsorption syndromes always require parenteral vitamin B,r. Folate deficiency can be treated with oral folic acid, 1 to 5 mg/d, until complete hematologic recovery; oral therapy is effective even in malabsorption conditions. DON'T BE TRICKED o ReticulocJrtosis (e.g., secondary to hemolysis) can increase the MCV. o Vitamin B,, deficiency can present with subacute combined degeneration of the spinal column (weakness, paresthesias, ataxia) without anemia or macrocytosis. o Folate supplementation can improve the anemia of 8,, deficiency but does not prevent the associated neurologic sequelae. Hemolytic Anemia Diagnosis Characteristic findings are anemia, splenomegaly, elevated reticuloclte count, elevated LDH and indirect bilirubin, decreased haptoglobin, and elevated MCV (caused by reticulocytosis). Hemolytic anemia can be either congenital or acquired. Congenital hemolytic anemias include hemoglobinopathies (sickle cell disease), disorders of the erythrocyte membrane (hereditary spherocy.tosis), enzyme defects (G6PD deficiency), and thalassemia syndromes. In acquired hemolytic anemia, hemolysis can occur secondary to medications (fludarabine, bendamustine, quinine, penicillins, o methyldopa); can be immune in nature; or can occur secondary to micro- or macroangiopathic processes, infections, or physical agents. Examining the peripheral blood smear is central to identifying erlthrocyte morphologies that implicate certain hemolytic mechanisms.

In acquired hemolytic anemia, hemolysis can occur secondary to medications (fludarabine, bendamustine, quinine, penicillins, o methyldopa); can be immune in nature; or can occur secondary to micro- or macroangiopathic processes, infections, or physical agents. Examining the peripheral blood smear is central to identifying erlthrocyte morphologies that implicate certain hemolytic mechanisms. STUDY TABLE: Peripheral Blood Smear Findings in Hemolytic Anemia Finding Diagnosis Sch istocytes a nd thrombocytopen ia TTP.HUS, DIC, HELLP Schistocytes in a patient with a prosthetic heart valve Valve leak Erythrocyte agglutination Cold agglutinin hemolysis (Mycoplasma infection, lymphoproliferative diseases, CLL) Spherocytes Autoimmune hemolytic anemia or hereditary spherocytosis Target cells Thalassemia or other hemoglobinopathy Sickle cells Sickle cell anemia Bite cells G6PD deficienry (suggested by eccentrically located hemoglobin confined to one side of the cell) 204

Hematology 5?UDY ?ABLE: Tests for Hemolytic Anemia Condition Test Cold agglutinin disease DAT (lgG negative, C3 positive) G6PD deficiency G6PD activity measurement (test 2-3 months after hemolytic event to detect deficiency) Hereditary spherocytosis Flow cytometry for eosin-S-maleimide binding to band 3 PNH Flow cytometry for CD55 and CD59 proteins Sickle cell disease, thalassemia, or other Hemoglobin electrophoresis hemoglobinopathy Warm autoimmune hemolytic anemia DAT (lgG positive, C3 positive or negative) Treatment All patients with sickle cell anemia or other hemolltic anemias require pneumococcal (both 23- and 13 valent), Haemophilus inf'luenzae type B, influenza, and meningococcal vaccinations. All patients with chronic hemolytic anemia require folic acid supplements. Severe symptomatic autoimmune anemia: transfusion even if fully matched erythrocltes are not available. Warm autoimmune hemolytic anemia: initial therapy is glucocorticoids. Cold agglutinin disease: primary therapy is cold avoidance or rituximab for persistent symptoms; glucocorticoids or splenec tomy are usually ineffective. TTP: emergent plasma exchange. Hereditary spherocytosis and transfusion-dependent thalassemias: splenectomy. Severe thalassemia: HSCT is standard therapy. Severe PNH: eculizumab or ravulizumab. DOil'T BE TRICKED . A personal or family history of anemia, jaundice, splenomegaly, or gallstones suggests hereditary spherocytosis. TEST YOURSEIF A previously healthy 2S-year old woman with a negative famiiy history has weakness and a palpable spleen. Hemoglobin concen- tration is7.2 gldLand the reticuloc)'te count is 9.8% of erythrocytes. Peripheral blood smear shows an occasional spherocyte. ANSWER: For diagnosis, choose DAT to establish diagnosis of autoimmune hemolytic anemia' For management, select glucocor- ticoids. Sickle Cell Disease Diagnosis The sickle cell syndromes can be diagnosed by hemoglobin electrophoresis. Most clinical findings in sickle cell disease are related to vaso occlusion from sickled erythrocytes. Characteristic laboratory findings include elevated reticulocyte, platelet, and leukocyte counts and sickle cells on a peripheral blood smear. 205

lnfectious Disease Treatment gTUDY TABLE: Drug Treatment for Skin and Soft Tissue lnfection Diagnosis Empiric Treatment Nonpurulent cellulitis or erysipelas without systemic signs of Oral penicillin, amoxicillin, cephalexin, dicloxacillin, clindamycin infection Nonpurulent cellulitis or erysipelas with systemic signs of infection lV penicillin, ceftriaxone, cefazolin, clindamycin Purulent cellulitis, mild to moderate severity Trimethopri m-sulfamethoxazole, doxycycl ine Purulent cellulitis with extensive disease or signs of systemic Vancomycin (lV) or linezolid (oral or lV), daptomycin, telavancin, toxicity ceftaroline lmpetigo Extensive disease, treat as nonpurulent cellulitis; limited disease, mupirocin (topical) Folliculitis (staphylococcal and pseudomonal) Spontaneous resolution is typical. Topical mupirocin, clindamycin, or retapamulin Human bites (clenched fist injury) Prophylactic therapy with amoxicillin-clavulanate (oral); ampici n-sulbactam (lV) for infected wounds IIi Animal bites (mild infection without systemic symptoms) Amoxicilli n-clavulanate (oral) Necrotizing fasciitis, myonecrosis on imaging, purple bullae, Surgical debridement and combination therapy such as or sloughing of skin vancomycin plus piperacillin-tazobactam or imipenem or meropenem; add clindamycin to either regimen Treat risk factors for recurrent cellulitis, such as lymphedema, tinea pedis, and chronic venous insufflciency

Animal bites (mild infection without systemic symptoms) Amoxicilli n-clavulanate (oral) Necrotizing fasciitis, myonecrosis on imaging, purple bullae, Surgical debridement and combination therapy such as or sloughing of skin vancomycin plus piperacillin-tazobactam or imipenem or meropenem; add clindamycin to either regimen Treat risk factors for recurrent cellulitis, such as lymphedema, tinea pedis, and chronic venous insufflciency DON'T BE TRICKED . Primary treatment for abscesses, furuncles, and carbuncles is incision and drainage. Gram stain and culture should be obtained when antibiotic administration is planned. . Skin abscesses may have higher cure rates when incision and drainage is accompanied by antibiotic treatment with MRSA coverage. IEST YOURSEIF A 60-year-old woman has a temperature of 3B.B "C (101.8'F). Her right thigh is swollen and extremely tender to palpation, with a 5 cm red patch in the middle of the tender area. She requires morphine for pain. ANSWER: For diagnosis, choose myonecrosis. For management, select urgent MRI followed by surgical debridement. A 20 year old college football player has a fever, furuncles, and associated cellulitis. ANSWER: For diagnosis, choose MRSA infection. For management, select treatment with trimethoprim sulfamethoxazole or doxycycline. Vibrio vulnificuslnfection: Deep tissue infection associated with hemor. lmpetigo: Erosions with golden'yellow rhagic bullae caused by V. vulnificus ina patient with cirrhosis. crusts confirm the presence of impetigo. 224

lnfectious Disease Treatment Remove sources of infection and toxin production and begin IV fluid resuscitation. Select penicillin plus clindamycin for streptococcal TSS. For methicillin-susceptible staphylococcal TSS, select nafcillin or oxacillin and clindamycin; for MRSA TSS, select vancomycin and clindamycin. DOil'' BE?RICKED . Do not select glucocorticoids to treat TSS. TESTYOURSELF A 2S-year-old man has epistaxis managed by nasal packing. The next day, he is confused, his temperature is 39.0 'C (i02.2 "F), and BP is 90/82 mm Hg. Erythema of his face, shoulders, and palms is present. The nasal packing is still in place. Serum creatinine and aminotransferase levels are elevated. ANSWER: For diagnosis, select staphylococcal TSS; for management, choose removal of the nasal packing and initiation of antibiotics. Community-Acquired Pneu monia Diagnosis Streptococcus pneumoniae is the most commonly identified bacterial cause of CAP in patients of all ages. CAP caused by Moraxella.andHaemophilus species occurs mainly in patients with chronic pulmonary disease. Atypical microorganisms that cause CAP include Mycoplasma pneumoniae and. Chlamydophila pneumonioe and are more common in persons aged 20 to 40 years. Testing Sputum Gram stain and culture o patients admitted to the ICU o patients not responding to outpatient antibiotic therapy o patients with cavitary lung lesions . patients with underlying structural lung disease Blood culture o patients admitted to ICU o patients treated empirically for MRSA or Pseudomonas aeruginoso (negative result may allow de-escalation of antibiotic therapy) Rapid nucleic acid amplification tests for influenza r all patients hospitalized with CAP during influenza season Urine pneumococcal antigen and Legionellc antigen . all patients admitted to ICU o consider in patients admitted to ward 226

lnfectious Disease Treatment The Pneumonia Severity Index (PSI) and Infectious Disease Society of America/American Thoracic Society (IDSA/ATS) scoring systems help predict site of care. STUDY TABLE: CAP Clinical Decision Support Scoring Systems for Site of Care PSl. IDSA/ATSb Age >50 years Major criteria Comorbidities Need for mechanical ventilation Malignancy Septic shock requiring vasopressors Congestive heart failure Minor criteria Cerebrovascular disease Respiration rate >30/min Kidney disease Temperature <36.8'C (96.8 "F) Liver disease Hypotension requiring aggressive fluid resuscitation Vital signs Confusion or disorientation Heart rate >125lmin BUN >20 mg/dL(>7.1 mmol/L) Respiration rate >30/min Leukocyte count <4000/pL (4 x 1 Oell) Temperature <35 "C (95 "F) or >40 "C ( 1 04 'F) Platelet count <1 00,000/pL ( 1 00 x 1 Oell) SBP <90 mm Hg Po2/Fto2 ratio <250 Physical examination Multilobar in{iltrates Altered mentation ATS =American Thoracic Society; IDSA= lnfectious Diseases Society ofAmerica; PSI = Pneumonia Severity lndex. complex Step 2 scale (not shown) into risk class ll V judgment, is recommended to guide the need for higher levels of care. Empiric therapy for MRSA should be considered in patients with one of these risk factors:

STUDY TABLE: CAP Clinical Decision Support Scoring Systems for Site of Care PSl. IDSA/ATSb Age >50 years Major criteria Comorbidities Need for mechanical ventilation Malignancy Septic shock requiring vasopressors Congestive heart failure Minor criteria Cerebrovascular disease Respiration rate >30/min Kidney disease Temperature <36.8'C (96.8 "F) Liver disease Hypotension requiring aggressive fluid resuscitation Vital signs Confusion or disorientation Heart rate >125lmin BUN >20 mg/dL(>7.1 mmol/L) Respiration rate >30/min Leukocyte count <4000/pL (4 x 1 Oell) Temperature <35 "C (95 "F) or >40 "C ( 1 04 'F) Platelet count <1 00,000/pL ( 1 00 x 1 Oell) SBP <90 mm Hg Po2/Fto2 ratio <250 Physical examination Multilobar in{iltrates Altered mentation ATS =American Thoracic Society; IDSA= lnfectious Diseases Society ofAmerica; PSI = Pneumonia Severity lndex. complex Step 2 scale (not shown) into risk class ll V judgment, is recommended to guide the need for higher levels of care. Empiric therapy for MRSA should be considered in patients with one of these risk factors: o previous treatment for MRSA infection (strongest risk factor) o hospitalization or parenteral antibiotic administration in the preceding 90 days . preceding influenza-like illness . a suspicious Gram stain (gram-positive cocci in clusters) o conventional therapy failure . injection drug use or pleural-based lung nodules (suggesting septic pulmonary emboli) o cavitary lung lesions

o previous treatment for MRSA infection (strongest risk factor) o hospitalization or parenteral antibiotic administration in the preceding 90 days . preceding influenza-like illness . a suspicious Gram stain (gram-positive cocci in clusters) o conventional therapy failure . injection drug use or pleural-based lung nodules (suggesting septic pulmonary emboli) o cavitary lung lesions Pseudomonas should be considered in: o infection with this bacterium in the preceding year (strongest risk factor) o immunocompromised patients o patients with underlying structural lung disease (bronchiectasis or cystic fibrosis) . medical conditions requiring repeated courses of antibiotics . hospitalization or parenteral antibiotic administration in the preceding 90 days Anaerobic infections are uncommon causes of CAP. For patients in whom a concern exists for aspiration who can be treated in the ambulatory setting, amoxicillin or amoxicillin clavulanate is recommended. In hospitalized patients with CAB the addition of anaerobic coverage is recommended only if lung abscess or empyema is present. Patients with CAP who test positive for influenza should also be treated with an antiviral agent regardless of duration of illness before diagnosis. 227

lnfectious Disease For patients with uncomplicated CAP who demonstrate rapid defervescence and clinical improvement over the first 3 days, a S-day course of therapy is adequate for cure. Exceptions to short antibiotic course (3-5 days) include: . patients with cavitary disease or lung abscess, empyema . concomitant bacteremia o extrapulmonaryinfection . ongoing instability (persistent fever, abnormal vital signs, or hypoxia)

For patients with uncomplicated CAP who demonstrate rapid defervescence and clinical improvement over the first 3 days, a S-day course of therapy is adequate for cure. Exceptions to short antibiotic course (3-5 days) include: . patients with cavitary disease or lung abscess, empyema . concomitant bacteremia o extrapulmonaryinfection . ongoing instability (persistent fever, abnormal vital signs, or hypoxia) Site of Treatment Patient or Epidemiologic Most Common Regimens(s) Considerations Organisms Outpatient Healthy patient without S. pneumoniae Amoxicillin risk factors for MRSA or Mycoplasma OR P aeruginosa Chlamydophila Doxycycline H ae mo phi lu s i nflu e nzae OR Respiratory viruses Macrolide (if local pneumococcal resistance <257") Comorbidities" Same as above Respiratory fl uoroquinoloneb OR Oral p-laaam'plus either a macrolide or doxycycline lnpatient, non-lCU' S. pneumoniae lntravenous p-laaamd plus a macrolide Mycoplasma OR

Site of Treatment Patient or Epidemiologic Most Common Regimens(s) Considerations Organisms Outpatient Healthy patient without S. pneumoniae Amoxicillin risk factors for MRSA or Mycoplasma OR P aeruginosa Chlamydophila Doxycycline H ae mo phi lu s i nflu e nzae OR Respiratory viruses Macrolide (if local pneumococcal resistance <257") Comorbidities" Same as above Respiratory fl uoroquinoloneb OR Oral p-laaam'plus either a macrolide or doxycycline lnpatient, non-lCU' S. pneumoniae lntravenous p-laaamd plus a macrolide Mycoplasma OR Chlamydophila Respiratory fluoroquinolone H. influenzae

Site of Treatment Patient or Epidemiologic Most Common Regimens(s) Considerations Organisms Outpatient Healthy patient without S. pneumoniae Amoxicillin risk factors for MRSA or Mycoplasma OR P aeruginosa Chlamydophila Doxycycline H ae mo phi lu s i nflu e nzae OR Respiratory viruses Macrolide (if local pneumococcal resistance <257") Comorbidities" Same as above Respiratory fl uoroquinoloneb OR Oral p-laaam'plus either a macrolide or doxycycline lnpatient, non-lCU' S. pneumoniae lntravenous p-laaamd plus a macrolide Mycoplasma OR Chlamydophila Respiratory fluoroquinolone H. influenzae Legionella Respiratory viruses ICU treatment S. pneumoniae lntravenous p-lactamd plus a macrolide; if contraindicated, p-lactam plus 5. aureus respiratory fluoroquinolone is an H. influenzae acceptable alternative

Legionella Respiratory viruses ICU treatment S. pneumoniae lntravenous p-lactamd plus a macrolide; if contraindicated, p-lactam plus 5. aureus respiratory fluoroquinolone is an H. influenzae acceptable alternative Legionella Gram-negative bacilli Any Risk factor for Pseudomonas Antipseudomonal p-lactam plus either (see text) a macrolide or an antipseudomonal quinolone Any Risk faaorfor CA-MRSA Standard therapy PLUS vancomycin (see text) OR linezolid CA-MRSA = community-acquired methicillin resistant Staphylococcus aureus. acomorbidities include chronic heart, lung, liver, or kidney disease; diabetes mellitus; alcoholism; asplenia; malignancies; and immunosuppression. 'Recommended oral p-lactams include amoxicillin-clavu anate, cefuroxime, or cefpodoxime. dRecommended parenteral p-lactams include ampicillin-sulbactam, ceftriaxone, or ceftaroline.

acomorbidities include chronic heart, lung, liver, or kidney disease; diabetes mellitus; alcoholism; asplenia; malignancies; and immunosuppression. 'Recommended oral p-lactams include amoxicillin-clavu anate, cefuroxime, or cefpodoxime. dRecommended parenteral p-lactams include ampicillin-sulbactam, ceftriaxone, or ceftaroline. Data from Metlay JP, Waterer GW, Long AC, et al. Diagnosas and treatment of adults with community,acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and lnfectious Diseases Society of America. Am J Respir Crit Carc Med.2O19;200:e45-e67. IPMID: 3 1 573350] doi:1 0.1 1 64lrccm.2O1 908 1 581 ST 228

lnfectious Disease DOil'T BE TRICKED o Glucocorticoids are not routinely recommended in CAP and should be reserved for patients with documented adrenal insufficiency or refractory septic shock. . Macrolides (azithromycin and clarithromycin) are recommended as monotherapy only for pneumonia in nonhospitalized patients if the regional prevalence of pneumococcal resistance to this class is known to be less than 25"1,. . Macrolides and quinolones may prolong the QT interval, and alternative agents should be considered in patients at risk for torsades de pointes, including those with a history of a long QT interval, those taking other medications that can prolong the QT interval, and those with electrolyte abnormalities. . Follow-up chest x ray is not routine; consider in adults aged >50 years with risk factors for lung cancer. Lyme Disease Prevention Indications for antibiotic prophylaxis: o tick is black-legged deer tick . attached >36 hours o antibiotics can be started within <72 hours of tick removal o patient is not pregnant or lactating Diagnosis Lyme disease is endemic to the northeast, mid Atlantic, and Midwest United States. It has three stages (early, disseminated, and late).

Lyme Disease Prevention Indications for antibiotic prophylaxis: o tick is black-legged deer tick . attached >36 hours o antibiotics can be started within <72 hours of tick removal o patient is not pregnant or lactating Diagnosis Lyme disease is endemic to the northeast, mid Atlantic, and Midwest United States. It has three stages (early, disseminated, and late). Sf UDY TABLE: Common Manifestations of Lyme Disease by Stage Stage Findings Management Early localized Within 30 days of exposure: erythema migrans Treat without serologic confirmation Early disseminated Weeks to months after exposure: flu-like illness, Treat if erythema migrans is present multiple erythema migrans lesions, heart ln absence of erythema migrans, obtain ELISA. lf positive conduction block, cranial neuropathy, or equivocal, obtain Western blot or different ELISA. lf rad iculoneuropathy, lymphocytic mening itis Western blot or second ELISA is positive, treat Late disseminated Months to years after exposure: monoarticular Treat if tvvo-tier serologic testing (above) is positive or oligoarlicular arthritis DOITI'T BE TRICKED e Do not test for Lyme disease in patients with nonspecific symptoms of fatigue, myalgia, arthralgia, or flbromyalgia in the absence ofexposure history or appropriate clinical findings. STUDY ?ABLE: Treatment of Lyme Disease by Stage Stage Treatment Choices Early localized disease Doxycycline for 10-21 days (preferred), amoxicillin, or cefuroxime for 14-21 days Early disseminated disease lV penicillin or ceftriaxone for 28 days Treat isolated facial nerve palsy same as early localized disease Late disseminated disease Same as early localized disease but for 28 days 229

lnfectious Disease DOil'T BETRICKED . Do not select the diagnosis "chronic Lyme disease." . Do not treat post-Lyme disease syndrome (fatigue, arthralgia, myalgia, memory disturbance) with antibiotics. . Do not rely on serologic test results to decide on the adequacy oftreatment. . Do not prescribe doxycycline for pregnant women. Erythema Migrans: A large erythematous ring characterizes erythema migrans and early Lyme Babesiosis disease. Diagnosis Babesiosis is a tick-borne (black-legged deer tick) malaria-like illness endemic to the northeast coast of the United States. Mild cases present with a flu-like illness. Testing Hemolytic anemia is the hallmark finding. Severe disease may be associated with thrombocytopenia, elevated aminotransferase levels, and AKI. A Wright- or Giemsa-stained peripheral blood (l smear will show intraerythroc,,tic parasites in ring or tetrad formations (Maltese cross shape). ,lur Babesiosis: Peripheral blood smear that shows intraerythrocytic parasites ananged in tetrads, resembling a Maltese cross. Treatment When Bcbesio infection is detected in an asymptomatic patient, monitoring for resolution of parasitemia without treatment is recommended for 3 months. Atovaquone plus azithromycin is the treatment of choice for patients with persistent parasitemia after 3 months and for mild to moderate symptomatic disease. In severe disease, select clindamycin plus quinine. Ehrlichiosis and Anaplasmosis Diagnosis Ehrlichia chaffeensis causes human monocytic ehrlichiosis (HME), and Anoplosma phagocytophilum causes human granulocSrtic anaplasmosis (HGA). Ehrlichiosis and anaplasmosis are spread by ticks. The clinical syndromes of HME and HGA are very similar: o fever, headache, and myalgia . multiorgan failure (AKI, ARDS, meningoencephalitis) r elevatedaminotransferases 230

Nephrology Treatment Treatment is directed at free water replacement and correction of the underlying problem leading to hypotonic fluid loss' The water deficit is calculated as [(Na* - l4o)174o] x TBW, where TBW = 0.5 x weight (kg) in women or 0'6 x weight (kg) in men' Correct the water deficit over 48 to 72 hours. In volume depletion, fluid resuscitation with normal saline should precede correction of the water deficit with hypotonic fluids. Neurogenic (central) DI is treated with intranasal or oral desmopressin. Hyperkalemia Diagnosis The most common causes of hyperkalemia include: . hyporeninemic hypoaldosteronism (type 4 [hyperkalemic distal] RIA; commonly seen among patients with diabetes) o acute and chronic kidney failure o low urine flow states o medications (ACE inhibitors, ARBs, potassium sparing diuretics, pentamidine, trimethoprim-sulfamethoxazole, and cyclosporine) o potassium shifts (rhabdomyolysis, hemolysis, hyperosmolality, insulin deficiency, p-adrenergic blockade, and metabolic acidosis) The earliest ECG changes of hyperkalemia are peaking of the T waves and shortening of the QT interval. As hyperkalemia progresses, the PR interval is prolonged, a loss of P waves occurs, and eventual widening of the QRS complexes is seen with a "sine-wave" pattern that may precede asystole. Pseudohyperkalemia is an in vitro phenomenon caused by the mechanical release of potassium from cells during phlebotomy or specimen processing or in the set- ting of marked leukocytosis and thrombocytosis. In patients with pseudohyper- 11 kalemia, the plasma potassium concentration is normal. I I 1- DO]I'T BE TRICKED I F I

DO]I'T BE TRICKED I F I . Significant hyperkalemia associated with a normal ECG suggests pseudohyperkalemia. -a , i :

. Significant hyperkalemia associated with a normal ECG suggests pseudohyperkalemia. -a , i : Treatment II t: ;ll If hyperkalemia is associated with ECG changes or arrhythmias, begin IV calcium I t q gluconate to stabilize the myocardium. Use insulin and glucose or inhaled -1 B adrenergic agonists to shift potassium inside the cells. Remove potassium from the t ! body with loop diuretics (particularly if the patient is volume overloaded), patiromer, { or sodium zirconium cyclosilicate, and institute dietary potassium restriction. I -1 Hemodialysis is often needed to correct life-threatening hyperkalemia but is ! - never the 'flrst step" because of the time delay in initiating dialysis. I f H = !t F T

Treatment II t: ;ll If hyperkalemia is associated with ECG changes or arrhythmias, begin IV calcium I t q gluconate to stabilize the myocardium. Use insulin and glucose or inhaled -1 B adrenergic agonists to shift potassium inside the cells. Remove potassium from the t ! body with loop diuretics (particularly if the patient is volume overloaded), patiromer, { or sodium zirconium cyclosilicate, and institute dietary potassium restriction. I -1 Hemodialysis is often needed to correct life-threatening hyperkalemia but is ! - never the 'flrst step" because of the time delay in initiating dialysis. I f H = !t F T DOil'T BETRICKED . Absolute levels of potassium cannot reliably determine whether a Characteristirs of Hyperkalemia: ECG showing flattened life-threatening condition exists. Only ECG can assess the effect of P waves; prolonged PR interval; widened 0RS; and tall, hyperkalemia on the cardiac membrane. peaked T waves characteristic of hyperkalemia.

DOil'T BETRICKED . Absolute levels of potassium cannot reliably determine whether a Characteristirs of Hyperkalemia: ECG showing flattened life-threatening condition exists. Only ECG can assess the effect of P waves; prolonged PR interval; widened 0RS; and tall, hyperkalemia on the cardiac membrane. peaked T waves characteristic of hyperkalemia. 264

Nephrology Treatment Treatment varies according to the specific findings. Kidney stones <S mm in diameter typically pass spontaneously. Stones >10 mm often require invasive measures. Patients with 6- to 10-mm stones may be treated with tamsulosin, nifedipine, silodo- sin, and tadalafil to enhance stone expulsion, but efficacy is controversial. Because few adverse effects are attributed to these medications, they are often recommended. Urgent urologic consultation is indicated for patients with: . pyelonephritis or urosepsis r AKI . large stones requiring surgical removal . bilateralobstruction o obstruction of a solitary kidney Urologic referral is also indicated for ambulatory patients without an immediate indication for stone removal who do not pass stones with conservative management or who have stones >10 mm in diameter. STUDY TABLE: Kidney Stone Risk Factors and Therapy Stone Type Risk Factors Therapy Calcium oxalate Clinical: hyperparathyroidism; fat malabsorption; excess vitamin lncrease fluids DorC Decrease sodium intake Biochemical: hypercalciuria; hyperoxaluria; hypocitraturia Maintain adequate dietary calcium Thiazide diuretics Calcium phosphate Clinical: distal renal tubular acidosis; hyperparathyroidism; carbonic lncrease fluids anhydrase inhibitors Decrease sodium intake Biochemical : elevated urine pH; hypercalciuria; hypocitratu ria Maintain adequate dietary calcium Thiazide diuretics Treat hyperparathyroidism

STUDY TABLE: Kidney Stone Risk Factors and Therapy Stone Type Risk Factors Therapy Calcium oxalate Clinical: hyperparathyroidism; fat malabsorption; excess vitamin lncrease fluids DorC Decrease sodium intake Biochemical: hypercalciuria; hyperoxaluria; hypocitraturia Maintain adequate dietary calcium Thiazide diuretics Calcium phosphate Clinical: distal renal tubular acidosis; hyperparathyroidism; carbonic lncrease fluids anhydrase inhibitors Decrease sodium intake Biochemical : elevated urine pH; hypercalciuria; hypocitratu ria Maintain adequate dietary calcium Thiazide diuretics Treat hyperparathyroidism Uric acid Clinical: metabolic syndrome; gout; diarrheal illnesses; metabolic lncrease fluids acidosis Potassium citrate or bicarbonate Biochemical: Low urine pH; hyperuricosuria Acetazolamide Allopurinol Struvite Clinical: chronic urinary tract infections with urea-splitting organism Treat infection Biochemical: elevated urine pH Urologic intervention Cysti ne Clinical: strong family history; young age at onset lncrease fluids

Uric acid Clinical: metabolic syndrome; gout; diarrheal illnesses; metabolic lncrease fluids acidosis Potassium citrate or bicarbonate Biochemical: Low urine pH; hyperuricosuria Acetazolamide Allopurinol Struvite Clinical: chronic urinary tract infections with urea-splitting organism Treat infection Biochemical: elevated urine pH Urologic intervention Cysti ne Clinical: strong family history; young age at onset lncrease fluids Biochemical: elevated urine cysteine; low urine pH Potassium citrate or bicarbonate Acetazolamide DON'T BE TRICKED . Asymptomatic nonobstructing kidney stones found on imaging studies do not require urgent stone removal' . Do not select a low-calcium diet for patients with kidney stones. Calcium restriction does not prevent stones and may actually increase stone formation and contribute to bone demineralization. TESTYOURSELF A 35 year-old woman is evaluated for nephrolithiasis' She has a long history ofCrohn disease and has had several operations to remove portions of her ileum and colon. AITISWER: For diagnosis, select calcium oxalate stones secondary to increased oxalate absorption in the GI tract and subsequent hyperoxaluria. 283

Neurology Treatment Lifestyle changes that benefit patients include exercise and smoking cessation. High dose glucocorticoids (oral or IV) speed recovery from acute exacerbations, most effectively in acute optic neuritis. Treat fever and look for underlying infection before beginning glucocorticoids, because fever worsens symptoms of MS (pseudorelapse), and treatment of the underlying trigger will improve symptoms. After the first attack of a clinically isolated syndrome (optic neuritis, spinal cord syndrome, or brainstem cerebellar syndrome) , prescribe interferon beta, glatiramer acetate, or teriflunomide if brain imaging suggests MS. Disease-modifying therapy in relapsing remitting MS results in prevention of relapses and disability progression, may reduce mortality, and may prevent conversion to secondary progressive MS. Interferon beta and glatiramer acetate are often used first and are well tolerated; other agents may be more efficacious but are associated with significant adverse effects and are reserved for highly active relapsing remitting or progressive forms of MS. MS relapses that have no or minimal impact on function may simply be observed. Vitamin D added to interferon beta reduces the accumulation of MRI lesions and is recommended for all patients with MS. All patients should receive annual inactivated influenza vaccination and maintain their regular immunization schedule.

Disease-modifying therapy in relapsing remitting MS results in prevention of relapses and disability progression, may reduce mortality, and may prevent conversion to secondary progressive MS. Interferon beta and glatiramer acetate are often used first and are well tolerated; other agents may be more efficacious but are associated with significant adverse effects and are reserved for highly active relapsing remitting or progressive forms of MS. MS relapses that have no or minimal impact on function may simply be observed. Vitamin D added to interferon beta reduces the accumulation of MRI lesions and is recommended for all patients with MS. All patients should receive annual inactivated influenza vaccination and maintain their regular immunization schedule. STUDY TABI-E: Symptomatic Management in Multiple Sclerosis Symptom Nonpharmacologic Management Pharmacologic Management Spasticity Physical therapy, stretching, massage therapy Baclofen, benzodiazepines, cyclobenzaprine, tizanidine Neuropathic pain Exercise therapy, CBT, mind-body therapies, physical Carbamazepine, duloxetine, gabapentin, pregabalin, therapy, acupuncture topiramate Fatigue lnsomnia treatment, regular exercise Am a nta d i ne, a m pheta m i nes, a rmodaf i n i l, mod afi n i I Depression lndividual or group counseling Antidepressants (SN Rls, SSRIs) Cognitive Cognitive rehabilitation and accommodation strategies No proven therapy dysfunction Mobility Physical and occupational therapy; use of braces, canes, Dalfampridine rolling walkers, or electrostimulatory walk-assist devices Urinary retention Manual pelvic pressure, intermittent catheterization None Urinary urgency Bladder training, timed voiding Solifenacin, oxybutynin, tolterodine DON'T BE TRICKED o Interferon agents are contraindicated in patients with liver disease or depression. o Pregnancy does not cause additional permanent disability in women with MS. . Combining glatiramer acetate with interferon beta provides no added benefit to either drug alone.

STUDY TABI-E: Symptomatic Management in Multiple Sclerosis Symptom Nonpharmacologic Management Pharmacologic Management Spasticity Physical therapy, stretching, massage therapy Baclofen, benzodiazepines, cyclobenzaprine, tizanidine Neuropathic pain Exercise therapy, CBT, mind-body therapies, physical Carbamazepine, duloxetine, gabapentin, pregabalin, therapy, acupuncture topiramate Fatigue lnsomnia treatment, regular exercise Am a nta d i ne, a m pheta m i nes, a rmodaf i n i l, mod afi n i I Depression lndividual or group counseling Antidepressants (SN Rls, SSRIs) Cognitive Cognitive rehabilitation and accommodation strategies No proven therapy dysfunction Mobility Physical and occupational therapy; use of braces, canes, Dalfampridine rolling walkers, or electrostimulatory walk-assist devices Urinary retention Manual pelvic pressure, intermittent catheterization None Urinary urgency Bladder training, timed voiding Solifenacin, oxybutynin, tolterodine DON'T BE TRICKED o Interferon agents are contraindicated in patients with liver disease or depression. o Pregnancy does not cause additional permanent disability in women with MS. . Combining glatiramer acetate with interferon beta provides no added benefit to either drug alone. TESTYOURSELF A 25 year-old woman has a 2 week episode of new-onset gait ataxia, nystagmus, and dysarthria. Two years ago, she had optic neuritis. An MRI of the brain now shows brain lesions consistent with MS. ANSWER: Fordiagrrosis, choose relapsing remitting MS. For management, select IV methylprednisolone and interferon beta. Multiple Sclerosis lesions: tluid-attenuated inversion recovery MRI shows MS lesions in the paraventricular white matter bilaterally. 304

Neurology I Myelopathy Diagnosis Spinal cord dysfunction, or myelopathy, can occur because of a lesion arising within the spinal cord (intramedullary) or because of extrinsic compression of the spinal cord. Injury to the corticospinal tracts manifests as weakness, hyperreflexia, spasticity, and extensor plantar responses Involvement of the distal cord and lower roots (cauda equina syndrome) manifests as lower extremity weakness with decreased muscle tone and areflexia. Causes of noncompressive myelopathy include inflammatory or demyelinating lesions, spinal cord infarction, and copper or vitamin B,, deficiency. $TUfY TAtsl,Er Selected Causes of lntramedullary Myelopathy Cause Featules MS See Multiple Sclerosis Neuromyelitis Recurrent episodes of longitudinally extensive myelitis and optic neuritis without the brain lesions typical of MS; optica (Devic NMO-lgG autoantibody may be present disease) ldiopathic Subacute onset of weakness, sensory changes, and bowel/bladder dysfunction, typically after a viral infection transverse myelitis Distinguished from MS by the presence of complete myetitis, no oligoclonal bands or elevated lgG index in the CSF, and no lesions on brain MRI Vitamin 8,2 Paresthesias, lower-extremity weakness, and gait instability deficiency Findings may include paraparesis, vibration and position sense loss, and sensory ataxia. Anemia may be absent Copper Mimics vitamin B12 deficiency deficiency May develop after bariatric surgery or from excessive zinc ingestion lnfarction of the Acute onset of flaccid paralysis or weakness and pinprick sensation loss below the level of the infarction spinal cord Potential causes include emboli, hypotension during cardiovascular/aortic surgery, and AV malformations

Vitamin 8,2 Paresthesias, lower-extremity weakness, and gait instability deficiency Findings may include paraparesis, vibration and position sense loss, and sensory ataxia. Anemia may be absent Copper Mimics vitamin B12 deficiency deficiency May develop after bariatric surgery or from excessive zinc ingestion lnfarction of the Acute onset of flaccid paralysis or weakness and pinprick sensation loss below the level of the infarction spinal cord Potential causes include emboli, hypotension during cardiovascular/aortic surgery, and AV malformations Spinal cord compression most commonly presents with neck or back pain, followed by weakness, sensory changes, and bowel and bladder dysfunction associated with upper motoneuron signs (weakness, spasticity, hyperreflexia, extensor plantar responses) and occasionally lower motoneuron signs (atrophy, hyporeflexia) at the level of the lesion. Clues to the cause o[compression myelopathy: . fever - epidural abscess . anticoagulation - epidural hematoma o cancer - metastases . trauma vertebral fracture . elderly with chronic back/leg pain - spinal stenosis Select MRI of the spine to exclude spinal cord compression in all patients with clinical suspicion of spinal cord disorder. LP may be beneficial in patients with suspected inflammatory or demyelinating spinal cord lesions. DON'T BE TRICKED . Check methylmalonic acid and homocysteine measurements for patients with borderline vitamin 8,, values. 305

Neurology Treatment Only pregabalin, duloxetine, and tapentadol (extended release) are FDA approved flor the treatment ofpainful neuropathy. DON'T BE TRICKED o When the presentation of Bell palsy is classic and without any additional neurologic deficits, brain imaging and routine laboratory testing are not necessary. . Do not treat Bell palsy with antiviral drugs. . Screening for glucose intolerance should be performed in all nondiabetic patients who have distal sensory neuropathy. . Glucocorticoids are not beneficial in Guillain-Barrd syndrome and may even slow the recovery. TESTYOURSELF A 37 year old woman has difficulty going up stairs. She had diarrhea and low grade fever 2 weeks ago. Physical examination shows weakness of both lower extremities and diminished deep tendon reflexes. ANSWER: For diagnosis, choose Guillain Barre syndrome. For management, select plasma exchange and IV immune globulin. Myopathy Myopathies typically present with symmetric weakness of the proximal muscles. o Normal sensory and reflex examination differentiates myopathy from neuropathy. . Serum CK level is elevated and falls in response to treatment. . EMG confirms the presence of myopathic changes (low amplitude, short duration, and polyphasic motor unit potentials). See Rheumatologr chapter for more detailed information on the inflammatory myopathies (polymyositis, dermatomyositis, inclusion body myositis). STUOY TABLE: Myopathy Diagnostic Features Condition Diagnostic Clues Hypothyroid Diffuse myalgia, proximal muscle weakness, delayed relaxation phase of deep tendon reflexes, and elevation of CK myopathy Hyperthyroidism Myopathy, brisk reflexes, fasciculation, and ophthal moplegia Vitamin D Proximal muscle weakness, myalgia, fatigue, and osteomalacia-related bone pain deficiency Glucocorticoid Proximalweakness and myalgia, normal CK levels, and normal EMG findings myopathy Statin myopathy Subacute toxic myopathy associated with rhabdomyolysis. The risk of myopathy increases with the addition of fenofibrate or gemfibrozil and the addition of cytochrome P-450 3A4 isozyme inhibitors. Myotonic Myotonia (manifested as delayed handgrip release) and distal weakness dystrophies

STUOY TABLE: Myopathy Diagnostic Features Condition Diagnostic Clues Hypothyroid Diffuse myalgia, proximal muscle weakness, delayed relaxation phase of deep tendon reflexes, and elevation of CK myopathy Hyperthyroidism Myopathy, brisk reflexes, fasciculation, and ophthal moplegia Vitamin D Proximal muscle weakness, myalgia, fatigue, and osteomalacia-related bone pain deficiency Glucocorticoid Proximalweakness and myalgia, normal CK levels, and normal EMG findings myopathy Statin myopathy Subacute toxic myopathy associated with rhabdomyolysis. The risk of myopathy increases with the addition of fenofibrate or gemfibrozil and the addition of cytochrome P-450 3A4 isozyme inhibitors. Myotonic Myotonia (manifested as delayed handgrip release) and distal weakness dystrophies DOil'T BE TRICKED . Lipophilic statins (atorvastatin, simvastatin, and lovastatin) have a higher propensity to cause statin myopathy compared with hydrophilic statins (fluvastatin, pravastatin, and rosuvastatin). 309

Oncology Treatment The three major treatment strategies for localized prostate cancer are surgery radiation therapy, and active surveillance. Active surveillance is the postponement of definitive local therapy coupled with surveillance using serum PSA measurement, digital rectal examination, and repeat prostate biopsy. Men undergoing active surveillance receive definitive local therapy ifany disease progression is evident. General rules for treating prostate cancer in most men: o Active surveillance is indicated for men with very low-risk cancer and a life expectancy >10 years. . Options for local therapy include external beam radiotherapy, brachytherapy, and radical prostatectomy. r After radiation therapy, intermediate or higher risk disease is treated with adjuvant ADT with a GnRH agonist (e.g., leu- prolide, goserelin). e For men with PSA recurrence, evaluation for clinical local or metastatic disease with imaging is indicated. . Men originally treated with surgery can be treated with radiation with or without ADT (orchiectomy, GnRH agonist therapy, GnRH antagonist therapy). . Men originally treated with radiation can be treated with surgery or cryotherapy and ADT. Metastatic disease: o Treat with ADT. . Response to ADT therapy defines castration-sensitive prostate cancer; consider chemotherapy. . Progression on ADT defines castration resistant prostate cancer; add chemotherapy. r Routinely add bisphosphonates or denosumab to reduce bone pain and fracture risk. o Treat symptomatic bone metastases with radiation (local disease) or radium-223 (widespread disease). Follow-up Prostate cancer therapies are associated with their own unique difficulties: o Radiation is associated with short term risks for enteritis and cystitis and increasing incidence of ED over time . Radical prostatectomy is associated with urinary incontinence and ED. o ADT is associated with bone loss, a possible increase in cardiovascular risk, and increased VTE risk. General principles of management: . Start supplemental calcium and vitamin D. . Obtain a DEXA scan, and treat accordingly. o Manage cardiovascular risk, including lipid levels and blood pressure.

o Radiation is associated with short term risks for enteritis and cystitis and increasing incidence of ED over time . Radical prostatectomy is associated with urinary incontinence and ED. o ADT is associated with bone loss, a possible increase in cardiovascular risk, and increased VTE risk. General principles of management: . Start supplemental calcium and vitamin D. . Obtain a DEXA scan, and treat accordingly. o Manage cardiovascular risk, including lipid levels and blood pressure. DO]I'T BE TRICKED . Survival is no different for patients with low-risk, localized prostate cancer treated with active surveillance, surgery, or radiation therapy. . Orchiectomy is a rapidly acting and cost-effective way to achieve androgen depletion. Testicular Cancer Diagnosis Characteristic findings include a testicular mass, testicular swelling and pain, weight loss, retroperitoneal lymphadenopathy, and metastatic pulmonary lesions. 324

Pulmonary and Critical Care Medicine Treatment STUDY TABLE: Treatment of Sepsis and Septic Shock Treatment Application Fluid resuscitation Balanced crystalloids 30 mUkg within first hour Subsequentfluid based on clinical assessment Vasopressors Norepinephrine Vasopressin (norepinephrine-spa ring agent) lndicated for persistent hypotension unresponsive to fluids Source identification and control Blood cultures, cultures of potential sites of infection, chest x-ray, urinalysis Antibiotic therapy lnitiate within t h of diagnosis Narrow coverage based on culture and sensitivity findings Carbapenem or extended-range penicillin/B-lactamase inhibitor in most patients; in cases of septic shock (but not sepsis without shock), combination therapy with at least two antibiotics from different classes to cover the most likely bacterial pathogen Hydrocortisone 200-400 mg/d lVfor persistent hypotension despite fluids and vasopressors Glucose control lnsulin therapy to maintain glucose between 140 and 180 mg/dL Mechanical ventilation Tidalvolume 4-8 mg/kg of ideal body weight if ARDS present DON'T BE TRICKED . Do not perform cortisol stimulation testing. . Do not use noninvasive ventilation. Nutritional Support during Critical lllness Diagnosis Nutrition is an essential part of management for patients in the ICU and can be given enterally or parenterally, with the enteral route preferred. Total parenteral nutrition is associated with GI mucosal atrophy and translocation of gut bacteria into the bloodstream, which predisposes patients to infection.

Nutritional Support during Critical lllness Diagnosis Nutrition is an essential part of management for patients in the ICU and can be given enterally or parenterally, with the enteral route preferred. Total parenteral nutrition is associated with GI mucosal atrophy and translocation of gut bacteria into the bloodstream, which predisposes patients to infection. Treatment Initiation of enteral nutrition is recommended at24to 48 hours following admission. Critically ill patients who cannot maintain volitional nutritional intake may be fed enterally. For patients who cannot tolerate enteral feeding, total parenteral nutrition should not be started before day 7 of an acute illness. However, parenteral nutrition should be started as soon as possible for severely malnourished patients and those at high risk of malnutrition when enteral nutrition is not possible. Caloric and protein needs should be gradually increased to their goal over the course of 3 to 7 days. ICU-Acquired Weakness Diagnosis ICU acquired weakness includes critical illness polyneuropathy (with axonal nerve degeneration) and critical illness myopathy (with muscle myosin loss), resulting in profound weakness. ICU acquired weakness may be first recognized when a patient is unable to be weaned from mechanical ventilation. Risk factors include hyperglycemia, sepsis, multiple organ dysfunction, and SIRS' 361

Rheumatology Treatment Treatment is for organ specific manifestations; no overall disease-modif,iing therapy is available. Raynaud phenomenon: Avoiding cold exposure and smoking reduces the risk of Raynaud episodes. Use amlodipine, felodipine, nifedipine, sildenafil, and nitroglycerin paste to manage symptoms. Gastric and intestinal dysmotility: Prescribe PPIs for GERD and promotility agents (metoclopramide) fbr gastric and intestinal dysmotility. Scleroderma renal crisis: Prescribe ACE inhibitors for scleroderma renal crisis regardless of the serum creatinine level; continue even in the setting ofkidney failure. Bacterial overgrowth: Prescribe rotating broad-spectrum antibiotics for bacterial overgrowth. Alveolitis: Treat active alveolitis or rapidly progressive interstitial lung disease with mycophenolate mofetil, cyclophosphamide, or nintedanib plus mycophenolate. PAH: Treat PAH similarly to idiopathic PAH. DOil'T BE TRICKED o Glucocorticoid therapy is a risk factor for scleroderma renal crisis and may be associated with normotensive renal crisis (AKI in the absence of hypertension); do not use glucocorticoids to treat scleroderma. TEST YOURSELF A S9-year-old woman has accelerated hypertension and CKD. She has a history of Raynaud phenomenon. BP is 160/122 mm Hg. Her fingers appear tapered, with very smooth skin and ulcers on the fingertips. Serum creatinine level is 5.4 mg/dl. ANSWER: For diagnosis, choose scleroderma renal crisis. For management, select an ACE inhibitor. Mixed Connective Tissue Disease MCTD is a specific syndrome that includes features of at least two of the following: SLE, SSc, and autoimmune myositis in the presence of anti- UI-RNP antibodies. Diagnosis In addition to RNP antibodies, clinical features of MCTD may include: . Raynaudphenomenon . edema ofthe hands . sclerodactyly . synovitis . myositis The mortality of patients with MCTD is largely attributable to PAH. DON'T BE TRICKED r Positive anti Sm or anti-dsDNA antibodies support the diagnosis of SLE, not MCTD 381